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1.
Biochem Pharmacol ; 212: 115545, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37044296

RESUMO

Long-standing scarcity of efficacious treatments and tumor heterogeneity have contributed to triple-negative breast cancer (TNBC), a subtype with a poor prognosis and aggressive behavior that accounts for 10-15% of all new cases of breast cancer. TNBC is characterized by the absence of progesterone and estrogen receptor expression and lacks gene amplification or overexpression of HER2. Genomic sequencing has detected that the unique mutational profile of both the somatic and germline modifications in TNBC is staggeringly dissimilar from other breast tumor subtypes. The clinical utility of sequencing germline BRCA1/2 genes has been well established in TNBC. Nevertheless, reports regarding the penetrance and risk of other susceptibility genes are relatively scarce. Recurring mutations (e.g., TP53 and PI3KCA mutations) occur together with rare mutations in TNBC, and the shared effects of genomic modifications drive its progression. Given the heterogeneity and complexity of this disease, a clinical understanding of the genomic modifications in TNBC can pave an innovative way toward its therapy. In this review, we summarized the most recent discoveries associated with the underlying biology of developmental signaling pathways in TNBC. We also summarize the recent advancements in genetics and epidemiology and discuss state-of-the-art vaccine-based therapeutic strategies for TNBC that will enable tailored therapeutics.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/terapia , Proteína BRCA1/genética , Epidemiologia Molecular , Proteína BRCA2/genética , Recidiva Local de Neoplasia
2.
Molecules ; 27(16)2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-36014376

RESUMO

The skin tissue of the scalp is unique from other skin tissues because it coexists with hair, and many differences in microbial composition have been confirmed. In scalp tissues, hair loss occurs due to a combination of internal and external factors, and several studies are being conducted to counteract this. However, not many studies have addressed hair loss from the perspective of the microbiome. In this study, subjects with hair loss and those with normal scalps were set as experimental and control groups, respectively. In the experimental group, hair loss had progressed, and there was a large difference in microbiome composition compared to the group with normal scalps. In particular, differences in Accumulibacter, Staphylococcus, and Corynebacterium were found. From Staphylococcus epidermidis Cicaria, two active components were isolated as a result of repeated column chromatography. Spectroscopic data led to the determination of chemical structures for adenosine and biotin. Fractions were obtained, and ex vivo tests were conducted using hair follicles derived from human scalp tissue. When the microbiome adenosine-treated group was compared to the control group, hair follicle length was increased, and hair root diameter was maintained during the experimental periods. In addition, the Cicaria culture medium and the microbial adenosine- and biotin-treated groups maintained the anagen phase, reducing progression to the catagen phase in the hair growth cycle. In conclusion, it was confirmed that the Cicaria culture medium and the microbial adenosine and biotin derived from the culture were effective in inhibiting hair loss.


Assuntos
Microbiota , Staphylococcus epidermidis , Adenosina , Alopecia , Biotina , Folículo Piloso , Humanos
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