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1.
Mol Oncol ; 17(4): 598-610, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36495126

RESUMO

Breast cancer is the leading cause of cancer death in Vietnamese women, but its mutational landscape and actionable alterations for targeted therapies remain unknown. After treatment, a sensitive biomarker to complement conventional imaging to monitor patients is also lacking. In this prospective multi-center study, 134 early-stage breast cancer patients eligible for curative-intent surgery were recruited. Genomic DNA from tumor tissues and paired white blood cells were sequenced to profile all tumor-derived mutations in 95 cancer-associated genes. Our bioinformatic algorithm was then utilized to identify top mutations for individual patients. Serial plasma samples were collected before surgery and at scheduled visits after surgery. Personalized assay tracking the selected mutations were performed to detect circulating tumor DNA (ctDNA) in the plasma. We found that the mutational landscape of the Vietnamese was largely similar to other Asian cohorts, showing higher TP53 mutation frequency than in Caucasians. Alterations in PIK3CA and PI3K signaling were dominant, particularly in our triple-negative subgroup. Using top-ranked mutations, we detected ctDNA in pre-operative plasma in 24.6-43.5% of the hormone-receptor-positive groups and 76.9-80.8% of the hormone-receptor-negative groups. The detection rate was associated with breast cancer subtypes and clinicopathological features that increased the risk of relapse. Interim analysis after a 15-month follow-up revealed post-operative detection of ctDNA in all three patients that had recurrence, with a lead time of 7-13 months ahead of clinical diagnosis. Our personalized assay is streamlined and affordable with promising clinical utility in residual cancer surveillance. We also generated the first somatic variant dataset for Vietnamese breast cancer women that could lay the foundation for precision cancer medicine in Vietnam.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Estudos Prospectivos , Fosfatidilinositol 3-Quinases/genética , População do Sudeste Asiático , Vietnã , Biomarcadores Tumorais/genética , Mutação/genética
2.
J Environ Radioact ; 139: 300-307, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24965965

RESUMO

The Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident resulted in extensive radioactive contamination of the environment via deposited radionuclides such as radiocesium and (131)I. Evaluating the extent and level of environmental contamination is critical to protecting citizens in affected areas and to planning decontamination efforts. However, a standardized soil sampling protocol is needed in such emergencies to facilitate the collection of large, tractable samples for measuring gamma-emitting radionuclides. In this study, we developed an emergency soil sampling protocol based on preliminary sampling from the FDNPP accident-affected area. We also present the results of a preliminary experiment aimed to evaluate the influence of various procedures (e.g., mixing, number of samples) on measured radioactivity. Results show that sample mixing strongly affects measured radioactivity in soil samples. Furthermore, for homogenization, shaking the plastic sample container at least 150 times or disaggregating soil by hand-rolling in a disposable plastic bag is required. Finally, we determined that five soil samples within a 3 m × 3-m area are the minimum number required for reducing measurement uncertainty in the emergency soil sampling protocol proposed here.


Assuntos
Acidente Nuclear de Fukushima , Monitoramento de Radiação/métodos , Cinza Radioativa/análise , Radioisótopos/análise , Poluentes Radioativos do Solo/análise , Japão
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