ABSTRACT
Human papillomavirus (HPV) infections are transmitted through sexual or other close contact and are etiologically associated with epithelial warts, papillomas, and intraepithelial lesions that may progress to cancer. Indeed, 4.8% of the global cancer burden is linked to HPV infection. Highly effective vaccines protect against two to nine of the most medically important HPV genotypes, yet vaccine uptake is inadequate and/or cost prohibitive in many settings. With HPV-related cancer incidence expected to rise over the coming decades, there is a need for effective HPV microbicides. Herein, we demonstrate the strong inhibitory activity of the heparin-neutralizing drug protamine sulfate (PS) against HPV infection. Pretreatment of cells with PS greatly reduced infection, regardless of HPV genotype or virus source. Vaginal application of PS prevented infection of the murine genital tract by HPV pseudovirions. Time-of-addition assays where PS was added to cells before infection, during infection, or after viral attachment demonstrated strong inhibitory activities on early infection steps. No effect on virus infection was found for cell lines deficient in heparan sulfate expression, suggesting that PS binds to heparan sulfate on the cell surface. Consistent with this, prophylactic PS exposure prevented viral attachment, including under low-pH conditions akin to the human vaginal tract. Our findings suggest PS acts dually to prevent HPV infection: prophylactic treatment prevents HPV attachment to host cells, and postattachment administration alters viral entry. Clinical trials are warranted to determine whether protamine-based products are effective as topical microbicides against genital HPVs.
Subject(s)
Papillomavirus Infections , Animals , Cell Line , Female , Humans , Mice , Papillomaviridae , Papillomavirus Infections/drug therapy , Papillomavirus Infections/epidemiology , Papillomavirus Infections/prevention & control , Protamines/pharmacology , Virus InternalizationABSTRACT
Papillomaviruses (PVs) were the first viruses recognized to cause tumors and cancers in mammalian hosts by Shope, nearly a century ago (Shope and Hurst, 1933). Over 40 years ago, zur Hausen (1976) first proposed that human papillomaviruses (HPVs) played a role in cervical cancer; in 2008, he shared the Nobel Prize in Medicine for his abundant contributions demonstrating the etiology of HPVs in genital cancers. Despite effective vaccines and screening, HPV infection and morbidity remain a significant worldwide burden, with HPV infections and HPV-related cancers expected increase through 2040. Although HPVs have long-recognized roles in tumorigenesis and cancers, our understanding of the molecular mechanisms by which these viruses interact with cells and usurp cellular processes to initiate infections and produce progeny virions is limited. This is due to longstanding challenges in both obtaining well-characterized infectious virus stocks and modeling tissue-based infection and the replicative cycles in vitro. In the last 20 years, the development of methods to produce virus-like particles (VLPs) and pseudovirions (PsV) along with more physiologically relevant cell- and tissue-based models has facilitated progress in this area. However, many questions regarding HPV infection remain difficult to address experimentally and are, thus, unanswered. Although an obligatory cellular uptake receptor has yet to be identified for any PV species, Rab-GTPases contribute to HPV uptake and transport of viral genomes toward the nucleus. Here, we provide a general overview of the current HPV infection paradigm, the epithelial differentiation-dependent HPV replicative cycle, and review the specifics of how HPVs usurp Rab-related functions during infectious entry. We also suggest other potential interactions based on how HPVs alter cellular activities to complete their replicative-cycle in differentiating epithelium. Understanding how HPVs interface with Rab functions during their complex replicative cycle may provide insight for the development of therapeutic interventions, as current viral counter-measures are solely prophylactic and therapies for HPV-positive individuals remain archaic and limited.
ABSTRACT
This article reviews the epidemiology, diagnosis, and management of vulvar preinvasive lesions, squamous cell carcinoma, and melanoma. There is an emphasis on sentinel lymph node dissection for early stage disease and advances in chemoradiation for late-stage disease. A brief review of vulvar Paget disease is also included.
Subject(s)
Carcinoma, Squamous Cell/therapy , Chemoradiotherapy , Melanoma/therapy , Paget Disease, Extramammary/therapy , Vulvar Neoplasms/therapy , Carcinoma, Squamous Cell/pathology , Female , Humans , Lymph Node Excision , Lymphatic Metastasis , Melanoma/pathology , Paget Disease, Extramammary/pathology , Sentinel Lymph Node Biopsy , Vulvar Neoplasms/pathologyABSTRACT
Resumen
Introducción: en México el uso de las terapias alternativas es popular. El personal de enfermería es por excelencia el educador del paciente y la familia; por lo tanto, sus actitudes y opiniones son relevantes acerca del uso de las TA.
Objetivo: conocer el uso de las terapias alternativas que hace el personal de enfermería y su opinión y actitudes en torno a ese uso con los pacientes y la familia.
Metodología: estudio descriptivo transversal, mediante el cual se le aplicaron 268 cuestionarios al personal de enfermería. El cuestionario fue diseñado ex profeso y validado para su aplicación.
Resultados: el 68% utilizó terapias alternativas y la mitad consideró que son seguras, el 27% mencionó que las recomienda a los pacientes y el 5% tuvo conocimiento del tema. El uso personal se asoció con la recomendación.
Conclusiones: la mayoría no indaga el antecedente del uso de terapias alternativas que hacen los pacientes. La recomendación de su uso se basa probablemente en la experiencia personal.
Abstract
Introduction: In Mexico the use of alternative therapies is popular. Par excellence, the nursing staff educates the patient and the family members; therefore, nursing staffs attitudes and opinions are relevant about the use of these therapies.
Objective: To know the use of alternative therapies by the nursing staff and their opinion and attitudes with patients and family concerning this use.
Methods: Cross-sectional descriptive study. 268 questionnaires were administered to the nursing staff. The questionnaire was designed with a purpose and validated.
Results: 68% of the nurse staff used alternative therapies, half believed these therapies are safe, 27% recommended them to patients, and 5% had knowledge of the subject. Personal use was associated with the recommendation.
Conclusions: The majority of the nursing staff does not investigate the antecedent of the use of alternative therapies by patients. The recommendation of its use is probably based on personal experience.
Subject(s)
Humans , Attitude , Attitude of Health Personnel , Data Collection , Cross-Sectional Studies , Nursing Staff , Complementary Therapies , Mexico , HumansABSTRACT
PURPOSE: To describe the relationship between retinoblastoma differentiation, histopathological risk factors, age at enucleation, laterality, and genetic type (hereditary or sporadic) in a series of enucleated eyes in a referral hospital. The criteria used in other studies to classify retinoblastoma differentiation are discussed. METHODS: The authors retrospectively studied histopathological preparations of eyes with retinoblastoma treated with primary enucleation. Tumors were classified as well differentiated, undifferentiated, and moderately differentiated. Patient age at enucleation, laterality of disease, genetic form (hereditary or sporadic), and presence of histopathological risk factors (massive choroidal infiltration, postlaminar optic nerve invasion, tumor in optic nerve cut, scleral invasion, and involvement of orbital soft tissues) were analyzed. The chi-square test was used for categorical variables and analysis of variance for test mean differences. RESULTS: Histopathological risk factors were present in 23 (36%) of 63 eyes. Moderately differentiated tumors occurred at advanced ages and were more frequently associated with histopathological risk factors. CONCLUSIONS: A consensus is needed to establish the histopathological criteria of retinoblastoma differentiation. The value of rosettes as a marker of cell differentiation should be reviewed.[J Pediatr Ophthalmol Strabismus 2013;50(3):174-177.].
Subject(s)
Neoplasm Staging/methods , Retinal Neoplasms/pathology , Retinoblastoma/pathology , Risk Assessment , Child, Preschool , Eye Enucleation , Female , Humans , Incidence , Infant , Male , Mexico/epidemiology , Prognosis , Retinal Neoplasms/epidemiology , Retinal Neoplasms/surgery , Retinoblastoma/epidemiology , Retinoblastoma/surgery , Risk FactorsABSTRACT
PURPOSE: To describe the types of complementary and alternative medicine (CAM) used by pediatric cancer patients attending a tertiary care hospital in Western Mexico. PATIENTS AND METHODS: In a cross-sectional survey, parents were interviewed and types of CAM employed as well as factors related to their use and their perceived effectiveness were determined. RESULTS: One hundred ten parents of pediatric cancer patients completed the survey. Seventy-seven patients (70%) received CAM. Of CAM used, herbal remedies (69%) and orally administered products (26%) were most common. Mean number of therapies was 2 +/- 1.1 (95% CI 1.59-2.12). Prior CAM use by the family was associated with use in patients (P = 0.006) (OR 4.6, CI 95% 1.7-12.9). Perceived usefulness was reported in 79% of CAM users. CONCLUSION: CAM use in Mexican children is common, most frequently with herbal therapies. The majority perceived benefits with its usage but in most cases, the treating physician was not informed about this practice.
Subject(s)
Neoplasms/drug therapy , Phytotherapy , Administration, Oral , Adolescent , Child , Child, Preschool , Cross-Sectional Studies , Female , Health Care Surveys , Humans , Infant , Male , Mexico , Phytotherapy/statistics & numerical data , Phytotherapy/trendsABSTRACT
A total of 119 children (1990-95) with acute lymphoblastic leukemia (ALL) B-lineage either CD10+or CD10- were registered into a single non-randomized chemotherapy protoco. Only untreated patients with standard risk were included in the study. Their ages ranges from 1.8-10 years with a mean of 5.1 years. There were 82 (68 percent) children with early pre B-All, 35 (29 percent) with pre B-All and 2 (1.6 percent) with transititional pre B-All (p<0.00001). The patients were divided according to CD10 reactivity, either + (94 children) or -(25 patients). The event-free survival (EFS) at 60 months for the CD10+children was of 78 percent (alive 73/94), while for the CD10- was 71 percent (alive 18/25) (p=0.6) and 74 percent for both groups. The factors that influenced favorably the survival in the CD10+group were the age between 3 to 5.99 years (p<0.00001), sex (either male or female), leukocyte count between 10.24.9 x 10-9/l (p<0.00001), LDH under 300 U/I (p<0.00001) and L1 bone marrow cytomorphology (p<0.00001). In the CD10- patients, the EFS was favorably influenced by the female sex (p=0.04), leukocyte count under 10 x 10-9/l (p=0.05) and LDH < 300 U/l (p=0.02). CNS infiltration was documented in 4.2 percent (5/119). Mortality secondary to chemotherapy was seen in 7 percent. In conclusion, this is the first large series in Mexican children with B-lineage ALL published. Because of the relatively small number of patients in each group (pre B and transitional pre B), all the patients in the current serieswere treated alike. When the 119 patients were divided only on the basis of CD10 reactivity, the EFS for both groups (CD10+ and') was similar; therefore, the reactivity to CD10 has no prognostic value in this type of ALL
Subject(s)
Humans , Male , Female , Child, Preschool , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Burkitt Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapyABSTRACT
El retinoblastoma (RB), constituye el tumor sólido más frecuente que presentan los pacientes que acuden al Instituto Nacional de Pediatría (INP) para atenderse. La presentación bilateral ocupa el 25 por ciento de los pacientes con RB. Se presentan algunas de las características epidemiológicas de la enfermedad bilateral con la intención de conocer las variables epidemiológicas más frecuentes en nuestra institución. Se revisaron los expedientes de 22 años del INP, en búsqueda de pacientes con RB bilateral investigando: sexo, edad, sincronía de la enfermedad bilateral, presencia de antecedentes familiares, etapa clínica de la enfermedad además de la presencia de segundas neoplasias. Existe predominio del sexo masculino 1.6:1.0 p=0.04 versus femenino. La distribución por estadio clínico quirúrgico fue: estadio retiniano 9/102 (9 por ciento), ocular 58/102 (57 por ciento), orbitario 26/102 (25 por ciento) y 9/102 (9 por ciento) no clasificables (p<0.00001). La forma asincrónica es rara en nuestra serie 16/105 (15 por ciento) p=0.00001. Los antecedentes heredofamiliares fueron positivos en 16/105 (15 por ciento). La frecuencia de segundas neoplasias encontradas fue 2/105 (0.01 por ciento). Por último, la forma asincrónica es inexistente en nuestra serie. No tenemos explicación etiológica posible para el número de casos tan elevados. La frecuencia de segundas neoplasias es inferior a las series reportadas aunque el seguimiento de estos casos deberá continuarse
