scholarly journals Case Report: Probable Cerebral Amyloid Angiopathy-Related Inflammation During Bevacizumab Treatment for Metastatic Cervical Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Tatiana Koudriavtseva ◽  
Svetlana Lorenzano ◽  
Vincenzo Anelli ◽  
Domenico Sergi ◽  
Annunziata Stefanile ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Endothelial Cells ◽  
Cerebral Amyloid Angiopathy ◽  
Vascular Endothelial Cells ◽  
Tumor Development ◽  
Amyloid Angiopathy ◽  
Vascular Endothelial ◽  
First Case ◽  
Bevacizumab Treatment ◽  
Cerebral Amyloid

Bevacizumab is an anti-angiogenic monoclonal antibody targeting Vascular Endothelial Growth Factor (VEGF) that induces the proliferation and migration of vascular endothelial cells thus, promoting vasculogenesis. Bevacizumab inhibits cancer angiogenesis, which is fundamental for either tumor development, exponential growth, or metastatic spread by supplying nutrients and oxygen. We report a new possible adverse event of bevacizumab, a Cerebral Amyloid Angiopathy-Related Inflammation (CAARI), in a 72-year-old woman with metastatic cervical cancer. After six cycles every three weeks of chemotherapy (cisplatin, paclitaxel, bevacizumab) and following two maintenance bevacizumab administrations, the patient presented a worsening confusional state. The MRI scan showed bilateral asymmetric temporo-parieto-occipital hyperintensity with numerous cortical microbleeds indicative of a CAARI. After stopping bevacizumab treatment, steroid therapy was administered resulting in rapid clinical improvement. The subsequent neurological and oncological follow-up was negative for recurrence. The patient was a heterozygote carrier for apolipoprotein-E ε4 that increases the risk of sporadic Cerebral Amyloid Angiopathy (CAA), which is characterized by beta-amyloid accumulation and fibrinoid necrosis in cerebral vasculature leading to micro/macrohemorrhages and dementia. Moreover, CAA is present in 30% of people aged over 60 years without dementia. In the brains of CAA patients, there is a proinflammatory state with cerebrovascular endothelial cell alteration and elevated levels of either adhesion molecules or inflammatory interleukins that increase the blood–brain barrier permeability. Moreover, CAARI is an inflammatory form of CAA. Inhibition of VEGF, which has anti-apoptotic, anti-inflammatory, and pro-survival effects on endothelial cells, impairs their regenerative capacity and increases expression of proinflammatory genes leading to weakened supporting layers of blood vessels and, hence, to damaged vascular integrity. In our patient, bevacizumab administration may have further increased permeability of cerebral microvasculature likely impaired by an underlying, asymptomatic CAA. To our knowledge, this is the first case reporting on the development of probable CAARI during bevacizumab treatment, which should alert the clinicians in case of neurological symptom onset in older patients under anti-angiogenic therapy.

Cerebral amyloid angiopathy-related inflammation during bevacizumab treatment for metastatic cervical cancer

2021 ◽  
Vol 429 ◽  
pp. 119954
Author(s):  
Tatiana Koudriavtseva ◽  
Svetlana Lorenzano ◽  
Vincenzo Anelli ◽  
Domenico Sergi ◽  
Annunziata Stefanile ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cerebral Amyloid Angiopathy ◽  
Amyloid Angiopathy ◽  
Bevacizumab Treatment ◽  
Cerebral Amyloid

scholarly journals Endothelial expression of human APP leads to cerebral amyloid angiopathy in mice

2020 ◽  
Author(s):  
Yuriko Tachida ◽  
Saori Miura ◽  
Rie Imamaki ◽  
Naomi Ogasawara ◽  
Hiroyuki Takuwa ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Vessels ◽  
Cerebral Amyloid Angiopathy ◽  
Amyloid Β ◽  
Blood Levels ◽  
Amyloid Angiopathy ◽  
Disease Mechanisms ◽  
Age Dependent ◽  
Cerebral Amyloid ◽  
The Brain

AbstractThe deposition of amyloid β (Aβ) in blood vessels of the brain, known as cerebral amyloid angiopathy (CAA), is observed in more than 90% of Alzheimer’s disease (AD) patients. The presence of such CAA pathology is not as evident, however, in most mouse models of AD, thereby making it difficult to examine the contribution of CAA to the pathogenesis of AD. Since blood levels of soluble amyloid precursor protein (sAPP) in rodents are less than 1% of those in humans, we hypothesized that endothelial APP expression would be markedly lower in rodents, thus providing a reason for the poorly expressed CAA pathology. Here we generated mice that specifically express human APP770 in endothelial cells. These mice exhibited an age-dependent robust deposition of Aβ in brain blood vessels but not in the parenchyma. Crossing these animals with APP knock-in mice led to an expanded CAA pathology as evidenced by increased amounts of amyloid accumulated in the cortical blood vessels. These results show that both neuronal and endothelial APP contribute cooperatively to vascular Aβ deposition, and suggest that this mouse model will be useful for studying disease mechanisms underlying CAA and for developing novel AD therapeutics.

scholarly journals Low Concentration of S100A8/9 Promotes Angiogenesis-Related Activity of Vascular Endothelial Cells: Bridges among Inflammation, Angiogenesis, and Tumorigenesis?

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Changyou Li ◽  
Siyuan Li ◽  
Changkai Jia ◽  
Lingling Yang ◽  
Zicheng Song ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial Cell ◽  
Tumor Development ◽  
Inflammatory Cells ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Low Concentration ◽  
Huvec Cells

Previous studies showed that several members of the S100A family are involved in neovascularization and tumor development. This study checked whether low concentrations of S100A8 or S100A9 has any effect on the behaviour of vascular endothelial cells. A human umbilical vascular endothelial cell (HUVEC) line was used to measure vascular endothelial cell bioactivity related to angiogenesis, such as cell proliferation, migration, and vessel formation. In the low concentration range up to 10 μg/mL, either each alone or in combination, S100A8 and S100A9 proteins promoted proliferation of HUVEC cells in a dose-dependent manner. The presence of both proteins in culture showed additive effects over each single protein. Both proteins enhanced HUVEC cells to migrate across the transwell membrane and to form tube-like structures on the Matrigel surface. When mixed in Matrigel and injected subcutaneously in Balb/c mice, both proteins increased vessel development in the gel plugs. Microarray assay of HUVEC cells treated with 10 μg/mL S100A8 revealed that ribosome pathway, pathogenicEscherichia coliinfection pathway, apoptosis, and stress response genes were modulated by S100A8 treatment. We propose that S100A8 and S100A9 proteins from either infiltrating inflammatory cells or tumor cells play an important role in the interplay among inflammation, angiogenesis, and tumorigenesis.

scholarly journals PSEN1 Compound Heterozygous Mutations Associated with Cerebral Amyloid Angiopathy and Cognitive Decline Phenotype

2021 ◽  
Vol 22 (8) ◽  
pp. 3870
Author(s):  
Ilaria Palmieri ◽  
Marialuisa Valente ◽  
Lisa Maria Farina ◽  
Simone Gana ◽  
Brigida Minafra ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Cognitive Decline ◽  
Cerebral Amyloid Angiopathy ◽  
Presenilin 1 ◽  
Compound Heterozygous ◽  
Amyloid Angiopathy ◽  
First Case ◽  
Cerebral Amyloid ◽  
Compound Heterozygous Mutations ◽  
The Impact

Cerebral amyloid angiopathy (CAA) is a cerebrovascular disorder caused by the deposition of amyloid beta-peptide (Aβ) aggregates. Aβ aggregates lead to vessel rupture and intracerebral hemorrhages, detected by magnetic resonance imaging (MRI). Presenile CAA is usually genetically determined by mutations in the amyloid precursor protein (APP) gene. However, mutations after codon 200 in the presenilin 1 (PSEN1) gene have been reported to facilitate CAA onset. Here, we analyzed the genetic bases in a patient of 55 years old affected by CAA and cognitive decline. DNA was isolated and genetic analysis was performed by Next-Generation Sequencing (NGS). RNA was extracted and retro-transcribed to perform segregation analysis by TOPO-TA cloning. WB analysis was carried out to check the impact of the mutations on protein. Two compound heterozygous mutations in PSEN1 exon 10, such as a novel stop-gain mutation (c.1070C > G) and a pathogenic splice variant (c.1129A > T), were found by NGS. Both mutations altered the presenilin 1 protein, truncating its C-terminal portion. This is the first case of CAA and cognitive decline caused by two compound mutations in PSEN1. With this report, we suggest extending the genetic analysis to PSEN1 when cerebral microbleeds are observed by MRI investigation in a patient affected by presenile cognitive decline.

scholarly journals Cerebral amyloid angiopathy-related inflammation (CAA-ri) in a patient positive for SARS-CoV-2 – radiological findings and differential diagnosis

2021 ◽  
Vol 3 (2) ◽  
pp. 37-40
Author(s):  
Marta Dębicka
Keyword(s):  
Differential Diagnosis ◽  
Cerebral Amyloid Angiopathy ◽  
Neurological Complications ◽  
Sudden Onset ◽  
Diagnostic Process ◽  
Amyloid Angiopathy ◽  
Impaired Consciousness ◽  
Radiological Findings ◽  
First Case ◽  
Cerebral Amyloid

84-year old female with confirmed, asymptomatic SARS-CoV-2 infection was admitted to Neurology Department after sudden onset of left-sided hemiparesis and impaired consciousness. Imaging played a key role in diagnostic process, in course of which the diagnosis of cerebral amyloid angiopathy-related inflammation (CAA-ri) was made. According to latest research, SARS-CoV-2 infection is considered to cause various neurological complications. To my best knowledge this is the first case of CAA-ri and SARS-CoV-2 coexistence to be reported.

Sign in / Sign up

Export Citation Format

Share Document