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1.
Cureus ; 14(10): e29901, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36348883

RESUMO

With declining maternal mortality rates in high-income countries (HICs), severe maternal morbidity (SMM) is becoming an important quality measure of maternal care. However, there is no international consensus on the definition and types of SMM. This study aims to critically analyze published literature on SMM in HICs. The objectives are to compare definitions and criteria used to identify SMM and identify the main causes and risk factors contributing to SMM in HICs. PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Scopus databases were searched for articles published between 2010 and 2022, results were filtered, and 10 studies were critically appraised. Six of the articles discussed SMM identification criteria and proposed definition modifications. Longer hospital stays and admission to the intensive care unit (ICU) were suggested as additional criteria. Disease-based criteria were shown to be superior to organ dysfunction criteria. Seven articles detailed common types of SMM as severe hemorrhage, hypertensive disorders, and preeclampsia/eclampsia. Six articles described SMM risk factors, of which advanced maternal age and cesarean delivery were the most common. This literature review identified disease-based criteria and Canadian study criteria as promising measures of SMM. It also identified several causes and risk factors of SMM common between HICs. These findings can help physicians identify women at risk of SMM. The study is however limited to eight HICs and 10 studies. Further research should aim to investigate how these criteria compare with previous sources of criteria and discern the association of weight and race risk factors with SMM.

2.
Cancer Res ; 79(16): 4057-4071, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31292163

RESUMO

Glioblastoma is the most common primary brain tumor in adults. While the introduction of temozolomide chemotherapy has increased long-term survivorship, treatment failure and rapid tumor recurrence remains universal. The transcriptional regulatory protein, inhibitor of DNA-binding-1 (ID1), is a key regulator of cell phenotype in cancer. We show that CRISPR-mediated knockout of ID1 in glioblastoma cells, breast adenocarcinoma cells, and melanoma cells dramatically reduced tumor progression in all three cancer systems through transcriptional downregulation of EGF, which resulted in decreased EGFR phosphorylation. Moreover, ID1-positive cells were enriched by chemotherapy and drove tumor recurrence in glioblastoma. Addition of the neuroleptic drug pimozide to inhibit ID1 expression enhanced the cytotoxic effects of temozolomide therapy on glioma cells and significantly prolonged time to tumor recurrence. Conclusively, these data suggest ID1 could be a promising therapeutic target in patients with glioblastoma. SIGNIFICANCE: These findings show that the transcriptional regulator ID1 is critical for glioblastoma initiation and chemoresistance and that inhibition of ID1 enhances the effect of temozolomide, delays tumor recurrence, and prolongs survival.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/fisiologia , Glioblastoma/tratamento farmacológico , Proteína 1 Inibidora de Diferenciação/metabolismo , Animais , Antineoplásicos Alquilantes/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Neoplasias da Mama/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Receptores ErbB/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Glioblastoma/mortalidade , Glioblastoma/patologia , Humanos , Proteína 1 Inibidora de Diferenciação/antagonistas & inibidores , Proteína 1 Inibidora de Diferenciação/genética , Melanoma/patologia , Camundongos Endogâmicos NOD , Fosforilação , Pimozida/administração & dosagem , Pimozida/farmacologia , Temozolomida/administração & dosagem , Temozolomida/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
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