Radiosurgery for brain metastases from ovarian cancer: an analysis of 25 years' experience with Gamma Knife treatment.

PURPOSE: We present our results in the treatment of brain metastases (BM) from ovarian cancer using Gamma Knife Radiosurgery (GKRS) over the last 25 years in a single institution. BACKGROUND: Gamma Knife Radiosurgery has become increasingly important in the management of brain metastases from ovarian cancer due to improving results from systemic disease and the need for better outcomes. MATERIAL AND METHODS: The medical records of 9 patients with brain metastases from ovarian cancer treated with GKRS between 1993 and 2018 were reviewed. Median age at first treatment was 57 years (range 39-76). Forty-two brain metastases were treated with 16 procedures. Median tumor volume was 1.8cc ranging from 0.2 to 30.3cc (there were five patients with a tumor volume exceeding 10cc). Median prescription dose was 16 Gy. RESULTS: Using Kaplan Meier estimates, the median OS after diagnosis was 48.1 months and the median OS after GKRS was 10.6 months (ranging from 2.5 to 81 months). The Kaplan Meier survival rates were 31.3%, and 6.5% at 2 and 5 years after GKRS, respectively. Treatment procedure was well tolerated and no patient presented with acute or chronic toxicity. Two of 9 patients had a tumor requiring retreatment (local control of 95% 40/42). Two out of the 7 patients evaluated for cause of death expired due to progression of brain metastases and the remaining ones died of systemic disease with brain control. CONCLUSIONS: GKRS for BM from ovarian cancer is a safe and effective modality. Our findings are in agreement with the recent literature indicating that women with brain metastases from ovarian cancer will benefit with radiosurgery and may achieve long term survival with brain control.

Williams' neural stem cells: new model for insight into microRNA dysregulation.

Williams syndrome (WS) is a neurodevelopmental genetic disorder, due to a 7q11.23 hemizygous deletion. WS has a characteristic neurocognitive profile that includes intellectual disability (ID). Haploinsufficiency of some of the deleted genes is partially associated with the cognitive phenotype. The aim of this paper is to determine the differences in the microRNA (miRNA) expression in WS patients, using a neural cell model from the patients olfactory neuroepithelium (ONE), and to establish the relationship with those genes involved in neurodevelopment and neural function. To assess these goals, we made a comparative analysis of the miRNAs expression profile between WS patients and controls. Through an in silico analysis, we established potential pathways and targets associated with neural tissue. The expression profile shows 14 dysregulated miRNAs, including nervous system (NS)-rich miRNAs such as miR-125b, let-7c and miR-200. Most of these miRNAs have potential targets associated with NS functions while others have been reported to have specific neuronal functions. These data suggest that miRNAs widely contribute to the regulation of neurodevelopmental intrinsic processes, and that specific miRNAs could participate in WS neurobiology.

Causas de diferimiento en la administración de quimioterapia a pacientes pediátricos ambulatorios / Causes of deferring chemotherapy administration to ambulatory pediatric patients

Introducción: La quimioterapia tiene indicaciones precisas, su diferimiento puede influir en el resultado del tratamiento, algunas causas son originadas por la situación clínica del paciente, otras médicas y administrativas. Objetivo: Identificar las principales causas que originan diferimiento en la administración de quimioterapia en pacientes pediátricos con cáncer. Metodología: Estudio observacional, prospectivo, se incluyeron 200 pacientes de un mes a 16 años 11 meses de edad, con enfermedades hemato-oncológicas. Se investigaron las causas de diferimiento mediante una lista de cotejo y observación directa durante tres meses. Las variables investigadas fueron: inasistencia del paciente al tratamiento, causas médicas, administrativas y situación clínica del paciente. El análisis estadístico se realizó con medidas de tendencia central. Resultados: El diferimiento de la administración de quimioterapia fue de 13.5%, la principal causa fue la inasistencia a la aplicación del tratamiento con 10.5%, seguido de la punción lumbar traumática 1.5% y neutropenia 1%. Discusión: En 5.5% de las ausencias no se obtuvo el motivo de la inasistencia. El diferimiento puede influir en el resultado del tratamiento ya que la no administración de los medicamentos de acuerdo al programa establecido puede favorecer el surgimiento de clonas resistentes a las drogas que se administran como quimioterapia, teniendo como consecuencia la pérdida del control de la enfermedad. Conclusiones: Se deben implementar estrategias con la ayuda del equipo multidisciplinario para localizar al paciente y recordar a sus padres la cita, así como sensibilizarlos de la importancia al cumplimiento del tratamiento en las fechas establecidas.

Introduction: Chemotherapy has precise indications; deferring it might influence the treatment outcomes. Some causes are originated for clinical situations of patients and others for medical or administrative reasons. Objective: To identify the main causes that deferring chemotherapy administration originates in pediatric patients with cancer. Methodology: Observational and prospective study included 200 patients from 11 months to 16 years and 11 months old with hemato-onchology disorders. Causes of deferring therapy were researched throughout a check list and direct observation during 3 months. The researched variables were: not showing up to the treatment visit, medical causes, administrative reasons, and clinical causes related to patients. Statistical analysis was done with measures of central tendency. Results: Causes of deferring chemotherapy administration were: 13.5% due to not showing up to the treatment visit with 10.5%, followed by 1.5% traumatic lumbar puncture, and 1% due to neutropenia. Discussion: The motive of not showing up in 5.5% was not obtained. Deferring might influence the treatment outcome because the lack of administration might favor the beginning of drug resistant colonies to chemotherapy, having as a consequence losing control of the disease. Conclusions: Some strategies should be implemented with the help of a multidisciplinary team to reach patients and remind their parents their appointment, as well as let them know about the importance of compliance of treatment in booked dates.

Enhanced oncogenicity of Asian-American human papillomavirus 16 is associated with impaired E2 repression of E6/E7 oncogene transcription.

Asian-American (AA) variants of human papillomavirus 16 (HPV-16) are linked to a high incidence of cervical cancer in Mexico, with some evidence strongly suggesting that they are more oncogenic than European (E) variants, including their association with younger women and their higher associated risk of cervical cancer. Differences in the regulation of viral E6/E7 oncogene transcription by the E2 protein may be involved in the higher oncogenicity of AA variants. In E variants, E6/E7 oncogene transcription is repressed by the E2 protein and is frequently up-regulated by the destruction of the E2 gene during viral integration. In contrast, the E2 gene is retained in full in most AA-positive carcinomas, raising the possibility of alternative mechanisms for increasing viral oncogene transcription. The authors investigated whether the higher oncogenicity of AA variants is linked to differences in E6/E7 oncogene transcription and the mechanism of E2 deactivation. E6/E7 and E1/E2 transcripts were explored by RT-PCR in 53 HPV-16-positive cervical carcinomas, 39 retaining (20 European and 19 AA) and 14 having lost (12 European and 2 AA) the E1/E2 genes, and transcription repression activity of the AA E2 genes was tested in four cell lines that constitutively express the beta-galactosidase reporter or E6/E7 genes driven by the viral long control region. E6/E7 oncogene transcripts were found in all carcinomas, but only those positive for AA variants with E1/E2 genes had complete E2 transcripts. E2 transcripts were down-regulated by splicing in E-positive carcinomas retaining E1/E2. AA E2 genes were impaired for repression of E6/E7 oncogene transcription in vivo. These results suggest that E6/E7 oncogene expression starts earlier in AA than E variant infections, since E variants need E2 to be destroyed or down-regulated.

Unbalanced collagenases/TIMP-1 expression and epithelial apoptosis in experimental lung fibrosis.

In this study, we examined the sequential expression of several matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and growth factors as well as the presence of apoptosis in a model of pulmonary fibrosis induced in rats with paraquat and hyperoxia. Animals showing neither clinical nor morphological changes with this double aggression were classified as "resistant". Rats were killed at 1, 2, 3, and 6 wk, and lungs were used for collagen content, gene expression by real-time PCR, gelatinolytic activity by zymography, apoptosis by in situ DNA fragmentation, and protein localization by immunohistochemistry. Our results showed a significant decrease of collagenases MMP-8 and MMP-13, with an increase of TIMP-1 and transforming growth factor-beta. Immunoreactive TIMP-1 was increased in experimental rats and primarily localized in alveolar macrophages. Expression of gelatinases MMP-2 and MMP-9 mRNAs was not affected, but lung zymography revealed an increase in progelatinase B, progelatinase A, and its active form. Epithelial apoptosis was evident from the first week, whereas at later periods, interstitial cell apoptosis was also noticed. Resistant animals behave as controls. These findings suggest that an imbalance between collagenases and TIMPs, excessive gelatinolytic activity, and epithelial apoptosis participate in the fibrotic response in this experimental model.