LRP1B Expression as a Putative Predictor of Response to Pegylated Liposomal Doxorubicin Treatment in Ovarian Cancer.

BACKGROUND: Pegylated liposomal doxorubicin (PLD) is among the most active therapies for recurrent/progressive ovarian cancer (OC). Low-density lipoprotein receptor-related protein 1B (LRP1B) is one of the 10 most significantly deleted genes in human cancers. It mediates endocytosis of several factors from the cellular environment including liposomes. Although the LRP1B role in cancer has not been fully disclosed, its contribution to resistance to liposomal therapies has been hypothesized. This study aimed to evaluate the impact of LRP1B protein as a possible marker of response to PLD in patients with OC. METHODS: LRP1B expression and response to PLD were analyzed in OC cell lines by qRT-PCR and PrestoBlue viability assay, respectively. LRP1B protein expression was evaluated for the first time, in tumor samples from PLD-treated patients and controls (other chemotherapies) by immunohistochemistry. Association of LRP1B staining score (determined based on intensity and percentage of positively stained cells) with clinicopathological features, response to therapy and survival outcomes was evaluated. RESULTS: OC cells with increased expression of LRP1B were more sensitive to PLD. LRP1B staining score was associated with clinicopathological features, response to therapy, and survival outcomes. Higher LRP1B levels were associated with prolonged progression-free survival. This association was more evident in patients treated with PLD and in responders to PLD. CONCLUSION: Our results support a possible role of LRP1B as a predictor of response to PLD in patients with OC.

The role of mifepristone on first trimester miscarriage treatment - A double-blind randomized controlled trial - MiFirsT.

OBJECTIVES: To evaluate the efficacy of combined mifepristone and misoprostol compared to misoprostol alone in outpatient medical treatment of first trimester miscarriage. Additionally, the study intends to compare the rate of complications, adverse effects, and treatment acceptability between groups. STUDY DESIGN: Single-center double-blind randomized placebo-controlled trial including women with diagnosis of missed first trimester miscarriage up to 9 weeks of gestation. RESULTS: Between April 2019 and November 2021, 216 women diagnosed with first trimester miscarriage up to 9 weeks of gestation were randomly assigned to mifepristone group or to misoprostol-alone group. Data from 105 women in mifepristone group and 103 women in misoprostol-alone group were analyzed, with no differences in baseline characteristics. The median time between medications (oral mifepristone/placebo and vaginal misoprostol) was nearly 43 h in both groups (p = 0.906). The median time to first follow-up was 2.6 weeks (IQR 1.0) in mifepristone group and 2.4 weeks (IQR 1.0) in misoprostol-alone group (p = 0.855). The overall success rate of medical treatment was significantly higher in the mifepristone-group comparing to misoprostol-alone group (94.3% vs. 82.5%, RR 1.14, 95% CI, 1.03-1.26; p = 0.008). Accordingly, the rate of surgical treatment was significantly lower in the mifepristone-group (5.7% vs.14.6%, RR 0.39, 95% CI, 0.16-0.97; p = 0.034). The composite complication rate was similar and lower than 4% in both groups. No case of complicated pelvic infection, hemodynamic instability or inpatient supportive treatment was reported. There were no significant differences in the rates of adverse events, median score for vaginal bleeding intensity or analgesics use. Despite the same median value, the score of abdominal pain intensity was significantly higher in the mifepristone-group (p = 0.011). In both groups, more than 65% of the women classified the treatment as "good" and 92% would recommend it to a friend on the same clinical situation. CONCLUSION: The mifepristone plus vaginal misoprostol combined treatment for medical resolution of first trimester miscarriage resulted in significant higher success rate and lower rate of surgical uterine evacuation comparing to misoprostol-alone treatment, with no relevant differences in adverse events or treatment acceptability.

Percepção de risco e comportamentos de proteção face à covid-19 em estudantes do ensino superior: o papel mediador do medo / Percepción del riesgo y conductas protectoras frente al covid-19 en estudiantes de enseñanza superior: el papel mediador del miedo / Risk Perception and Protective Behaviors Against covid-19 in Higher Education Students: The Mediating Role of Fea

O estudo tem como objetivo descrever os comportamentos de proteção adotados por estudantes portugue-ses do ensino superior durante a pandemia e analisar a sua relação com a percepção de risco e o papel mediador do medo face à covid-19. Participaram 335 estu-dantes com idades entre os 18 e os 29 anos (m= 21.42; dp= 2.43). Os participantes preencheram um inquérito sobre os comportamentos de proteção (i.e., preventi-vos e de evitamento), a percepção de risco e o medo face à covid-19. Os resultados demonstraram que os comportamentos preventivos mais utilizados foram a lavagem/desinfecção das mãos ao longo do dia e o uso de máscara na via pública ou espaços exteriores. Os comportamentos de evitamento mais adotados foram o de evitar locais com aglomeração e os convívios presenciais com colegas/amigos. Verificouse uma as-sociação positiva entre os comportamentos de proteção, a percepção de gravidade e o medo face à covid-19. O medo face à covid-19 foi mediador da relação entre a percepção de gravidade e os comportamentos preventivos (c' = .26, ic 95% [.11; .44]) e de evitamento (c' = .28, ic 95% [.12; .50]). Os resultados são discutidos aten-dendo ao papel da percepção de risco e do medo nas respostas comportamentais dos jovens, num contexto de pandemia, sendo apresentadas implicações práticas e sugestões para estudos futuros.

El estudio tiene como objetivo describir las conductas protectoras adoptadas por los estudiantes portugueses de educación superior durante la pandemia, y analizar su relación con la percepción de riesgo y el papel mediador del miedo al covid-19. Participaron en el estudio 335 estudiantes de entre 18 y 29 años (m = 21.42; ds = 2.43). Los participantes completaron una encuesta sobre conductas protectoras (es decir, preventivas y de evitación), percepción de riesgo y miedo al covid-19. Los resultados mostraron que las conductas preventivas más utilizadas fueron el lavado/desinfección de manos a lo largo del día y el uso de mascarilla en la vía pública o al aire libre. Los comportamientos de evitación más adoptados fueron evadir lugares con reuniones e interacciones cara a cara con compañeros/amigos. Hubo una correlación positiva entre las conductas protectoras, la percepción de seriedad y el miedo al covid-19. También se encontró que el miedo al covid-19 medió la relación entre la percepción de severidad y las conductas preventivas (c' = .26, ic 95% [.11; .44]) y de evitación (c' = .28, ic 95% [.12; .50]). Los resultados se discuten considerando el papel de la percepción del riesgo y el miedo en las respuestas conductuales de los jóvenes en un contexto pandémico, así mismo se presentan impli-caciones prácticas y sugerencias para estudios futuros.

The study aims to describe the protective behaviors adopted by Portuguese higher education students in during the and to analyze their relationship with the perception of risk and the mediating role of fear of covid-19. A total of 335 students aged be-tween 18 and 29 participated in the study (m= 21.42; sd = 2.43). Participants completed a survey on protective (i.e., preventive and avoidance) behaviors, risk perception, and fear of covid-19. The results showed that the most used preventive behaviors were hand washing/disinfection throughout the day and using masks in public streets or outdoor spaces. The most adopted avoidance behaviors were avoiding crowded places and face-to-face interactions with colleagues/friends. There was a positive correlation between pro-tective behaviors, the perception of severity, and fear of covid-19. Fear of covid-19 mediated the relation between the perception of severity and both preventive (c' = .26, ic 95% [.11; .44]) and avoidance (c' = .28, ic95% [.12; .50]) behaviors. The results are discussed considering the role of risk perception and fear in the behavioral responses of young people in a pandemic context while presenting practical implications and suggestions for future studies.

Centrosome amplification arises before neoplasia and increases upon p53 loss in tumorigenesis.

Centrosome abnormalities are a typical hallmark of human cancers. However, the origin and dynamics of such abnormalities in human cancer are not known. In this study, we examined centrosomes in Barrett's esophagus tumorigenesis, a well-characterized multistep pathway of progression, from the premalignant condition to the metastatic disease. This human cancer model allows the study of sequential steps of progression within the same patient and has representative cell lines from all stages of disease. Remarkably, centrosome amplification was detected as early as the premalignant condition and was significantly expanded in dysplasia. It was then present throughout malignant transformation both in adenocarcinoma and metastasis. The early expansion of centrosome amplification correlated with and was dependent on loss of function of the tumor suppressor p53 both through loss of wild-type expression and hotspot mutations. Our work shows that centrosome amplification in human tumorigenesis can occur before transformation, being repressed by p53. These findings suggest centrosome amplification in humans can contribute to tumor initiation and progression.

Dynamics of SOX2 and CDX2 Expression in Barrett's Mucosa.

Barrett's esophagus (BE) is the replacement of the normal esophageal squamous epithelium by a columnar lining epithelium. It is a premalignant condition for the development of adenocarcinoma of the esophagus and esophagogastric junction. BE is associated with gastroesophageal reflux which might change the expression profile of key transcription factors involved in the establishment of tissue differentiation, namely, SOX2 (associated with esophageal and gastric differentiation) and CDX2 (associated with intestinal differentiation). Here, we sought to characterize the expression profile of SOX2 and CDX2 in the sequential alterations of the esophageal mucosa towards adenocarcinoma and compare it with the well-established gastric and intestinal mucin profiles (MUC5AC, MUC6, and MUC2). We observed that SOX2 and CDX2 expression correlates with gastric and intestinal differentiation in BE, defined by morphological parameters and mucin expression. We show the presence of a complete intestinal profile in BE, without gastric mucins and without SOX2, and we observed an evolutionary modulation of the metaplastic phenotype by SOX2 and CDX2. We observed that adenocarcinomas harbor more frequently a mixed gastric and intestinal phenotype. In conclusion, our study establishes a role for transcription factors SOX2 and CDX2 in the progression from gastric to gastrointestinal differentiation in Barrett's metaplasia.