Effects of clinical heterogeneity on Pregnancy-Associated Breast Cancer survival: a systematic review with meta-analysis

Pregnancy-associated breast cancer is defined as a diagnosis of breast cancer during pregnancy or within 1 year of childbirth. Current evidence shows that Pregnancy-associated breast cancer is associated with poor prognosis; however, no systematic review has summarized and explored how baseline characteristics could impact survival. We aimed to explore the impact of breast cancer characteristics on death and disease relapse. A systematic review with meta-analyses was conducted by searching articles in the main databases (Medline, Embase, and Cochrane) and congress abstracts. Summarized death and disease-free survival hazard ratios were recalculated, and all meta-analyses used a random-effects model. Heterogeneity was reported using the I2 method. A total of 7143 studies were identified and only 30 studies were included. Pregnancy-associated breast cancer is associated with a 96% (HR 1.96; 95%CI 1.58­2.35) higher risk of death and 82% (HR 1.82; 95%CI 1.45­2.20) risk of death or disease relapse in comparison to a population of non-pregnancy-associated breast cancer or nulliparous breast cancer. Through sensitivity analyses, we identified that clinical outcomes were impacted, possibly due to Ki-67 levels, poorly differentiated tumors, and triple-negative breast cancer frequency in the study. As relevant sources of inconsistencies, such clinical cancer-related characteristics should be better investigated as potential confounders for upcoming Pregnancy-associated breast cancer therapeutic strategies.

MicroRNAs and exosomes: promising new biomarkers in acute myeloid leukemias?

ABSTRACT Despite advances in understanding of carcinogenesis and of treatment of acute myeloid leukemia, this neoplasm still has a lethality of at least 30%. The search for biomarkers that can predict the response to treatment in the early stages of the disease is still necessary. In recent years, a new form of cellular communication between tumor and non-neoplastic cells has been discovered: the exchange of information through extracellular vesicles. These are small vesicles released by membrane-coated cells that carry proteins, lipids, messenger RNAs, microRNA and DNA, which can be internalized and promote biological changes in target cells. Exosomes are qualified as a type of extracellular vesicle and, in tumors, carry immunoinhibitory signals that promote the escape of immune control. Recent studies have showed their involvement in communication with the cells of the tumor microenvironment and with chemoresistance in several tumors. To date, there is no information about immunoregulatory microRNAs transported by exosomes and their correlation with clinical evolution during chemotherapy for acute myeloid leukemia. Knowledge about immunomodulatory microRNAs obtained by leukemic cells and transported by exosomes can direct us towards the design of new diagnostic and treatment tools in this type of leukemia.

Comparative analysis between screening mammography performed in patients at usual risk and at high risk for breast cancer

Breast cancer is currently considered as a public health issue. To avoid late diagnosis, there is an attempt to use appropriate screening programs addressed to the early detection by testing the asymptomatic population in order to identify preclinical stage lesions. Methods: This is a retrospective, analytical, cross-sectional study of the notifications available in the cancer information system. The incidence of notifications from the reports of the BI-RADS™ notification system (Breast Imaging Reporting Data System) was compared between women at high and usual risk for breast cancer. Results: In the analyzed period, from 2013 to 2021, 16,065,383 screening mammographies were performed and notified in Brazil. Of these, 13,167,259 were performed in usualrisk women, whereas 2,898,124 were performed in high-risk women. To analyze the difference between reports of women at usual and high risk, the relative risk between them was calculated, as well as the necessary number to causa damage; the relative risk we found was of 0.5412 (95%CI 0.5341­0.5483) in B4 and relative risk of 0,433 (95%CI 0.4203­0.4462). As to the necessary number to cause damage, we observed 203 (95%CI 198­209) for B4 and 788 (95%CI 754­825) for B5. Despite the well-established need for breast cancer screening programs to reduce mortality, some aspects of screening do not have such a consensus. In this study, the incidence of reports that are suggestive of malignant breast lesions was higher among women at high risk.

Avaliação do papel da proteína PTX3 na lesão pulmonar induzida pela ventilação mecânica / Role of pentraxin 3 in ventilator-induced lung injury

Introdução: A ventilação mecânica (VM) é uma terapia indispensável no tratamento da insuficiência respiratória que pode causar como efeito colateral a Lesão Pulmonar Induzida pelo Ventilador (LPIV). Apesar do importante papel da inflamação na patogênese da LPIV, nem todos os mecanismos e vias são claramente conhecidos. O objetivo deste projeto foi investigar a função da proteína Pentraxina 3 (PTX3) na LPIV. Observamos que além de PTX3 ser um dos mediadores inflamatórios envolvidos na LPIV, sua presença em maiores quantidades levou ao desenvolvimento mais rápido da lesão nos animais transgênicos para Ptx3 em relação aos camundongos sem modificações quando submetidos à VM em alto volume corrente. A mesma ação pró-inflamatória de PTX3 não foi observada em condições de ventilação mecânica protetoras ao pulmão, sugerindo que seu impacto seja maior em LPIV mais severas. A fim de modular negativamente a expressão de PTX3 in vivo, investigamos a ação anti-inflamatória da Pentoxifilina na LPIV causada por alto volume corrente. Embora as doses de 50 e 100 mg/kg não tenham retardado o aparecimento da LPIV sua ação ainda deve ser melhor investigada. Nossos dados revelam o importante papel da pentraxina longa PTX3, cuja hiper-expressão acelerou o desenvolvimento da lesão pulmonar nos camundongos submetidos à ventilação mecânica. Os resultados contribuem para um melhor entendimento do processo inflamatório na LPIV e colaboram na elaboração de medidas visando minimizar tais danos...

Mechanical ventilation is an indispensable therapy for respiratory failure that can cause Ventilator-Induced Lung Injury (VILI) as side effect. Although inflammation is known to be involved in the pathogenesis of the ventilatorinduced lung injury (VILI), several aspects and mediators of this process are still unknown. This study aimed at investigating the role of the pentraxin 3 (PTX3) in VILI pathogenesis. In addition to be one of the inflammatory mediators in VILI, Ptx3 over-expression led to a faster development of VILI in Ptx3-transgenic mice in comparison with wild-type when submitted to high tidal volume ventilation. The same PTX3 pro-inflammatory action was not observed in a lung protective ventilation strategy, suggesting that its impact may be worse in more severe VILI. In order to down-regulate PTX3 expression in vivo, we investigated the Pentoxifylline anti-inflammatory action in VILI caused by high tidal volume ventilation. Although 50 and 100 mg/kg doses did not delayed the onset of VILI, its function deserves further investigation. Our data show the important involvement of the long pentraxin PTX3, which hiper-expression accelerated the lung injury development in mice submitted to mechanical ventilation. The results contribute to a better understanding of the inflammatory process in VILI disclosing the involvement of PTX3 in the pathogenesis of this disorder and its potential usefulness as a target for clinical interventions.