Familial Breast Cancer: Disease Related Gene Mutations and Screening Strategies for Chinese Population.

BACKGROUND: About 5%-10% of the breast cancer cases have a hereditary background, and this subset is referred to as familial breast cancer (FBC). In this review, we summarize the susceptibility genes and genetic syndromes associated with FBC and discuss the FBC screening and high-risk patient consulting strategies for the Chinese population. METHODS: We searched the PubMed database for articles published between January 2000 and August 2021. Finally, 380 pieces of literature addressing the genes and genetic syndromes related to FBC were included and reviewed. RESULTS: We identified 16 FBC-related genes and divided them into three types (high-, medium-, and low-penetrance) of genes according to their relative risk ratios. In addition, six genetic syndromes were found to be associated with FBC. We then summarized the currently available screening strategies for FBC and discussed those available for high-risk Chinese populations. CONCLUSION: Multiple gene mutations and genetic disorders are closely related to FBC. The National Comprehensive Cancer Network (NCCN) guidelines recommend corresponding screening strategies for these genetic diseases. However, such guidelines for the Chinese population are still lacking. For screening high-risk groups in the Chinese population, genetic testing is recommended after genetic counseling.

Metformin Inhibits Epithelial-to-Mesenchymal Transition of Keloid Fibroblasts via the HIF-1α/PKM2 Signaling Pathway.

Background: Epithelial-to-mesenchymal transition (EMT) is a process whereby epithelial cells lose cell-cell contacts and acquire expression of mesenchymal components and manifest a migratory phenotype. Recent studies indicated that EMT is involved in the development of keloids. Therefore, this study aims to investigate the mechanisms of the effects of metformin in hypoxia-induced EMT in keloid fibroblasts (KFs). Methods: KFs were cultured in a hypoxia incubator to induce EMT and were treated with or without metformin. Cell viability was evaluated by a cell counting kit 8 (CCK-8), and cell migration was measured by the transwell assay. The expression levels of HIF-1α, E-cadherin, vimentin, phosphorylated p70s6k (p-p70s6k) and pyruvate kinase M2 (PKM2) were evaluated by western blotting. Results: Hypoxia promoted EMT in KFs. Metformin significantly inhibited the expression of HIF-1α and partially abolished hypoxia-induced EMT. PKM2 is involved in hypoxia-induced EMT of KFs and metformin decreased the expression of p-p70s6k and PKM2. Conclusions: Metformin abolishes hypoxia-induced EMT in KFs by inhibiting the HIF-1α/PKM2 signaling pathway. Our study provides a novel mechanistic insight into potential use of metformin for treatment of keloids.

Clinical features, radiologic findings, and treatment of pediatric germ cell tumors involving the basal ganglia and thalamus: a retrospective series of 15 cases at a single center.

PURPOSE: Pediatric germ cell tumors (GCTs) involving the basal ganglia and thalamus are relatively rare neoplasms which have not been extensively described. We here summarize the clinical and radiological features of a series of such tumors and discuss optimal treatment strategies based upon our experience. METHODS: A total of 15 pediatric patients with basal ganglionic and thalamic GCTs were treated between 2011 and 2016 at West China Hospital. Epidemiological characteristics, clinical features, imaging findings, and treatment strategies were reviewed retrospectively. RESULTS: GCTs constituted 28% (15/53) of pediatric basal ganglionic and thalamic tumors in our institution between 2011 and 2016. There were 12 males and 3 females with mean age of 11.7 ± 2.8 years (range, 7-16 years). The most common initial manifestation was hemiparesis (n = 13, 86.7%), followed by headache (n = 5, 33.3%), vomiting (n = 3, 20.0%), cognitive disturbance (n = 2, 13.3%), and seizure (n = 1, 6.7%). No tumors were incidentally detected. The mean duration of the symptoms before diagnosis was 4.4 ± 3.9 months (range from 9 days to 13 months). The maximum diameters of the lesions ranged from 3.2 to 6.5 cm (mean 4.7 ± 1.1 cm). Cysts were seen in tumors in MRIs in 11 patients (73%), intratumoral hemorrhages in 3 (20%), calcification in 2 (13%), and there was obstructive hydrocephalus in 1 (7%). Of note, hemiatrophy was observed in 9 cases (60.0%). The mean follow-up for the 15 patients was 28 months (range, 9-54 months), and no patients were lost. During the follow-up period, all patients (9 cases) with germinomas responded well to radiotherapy, and no recurrence was observed. Among 4 patients with mixed nongerminomatous germ cell tumor, 2 suffered tumor recurrence after treatment. Neurological deficits improved or remained unchanged in 12 patients but 3 developed new dysfunction including significant cognitive disturbance and hemiparesis. CONCLUSIONS: Pediatric GCTs in the basal ganglia and thalamus are not as rare as previously considered. Tumor markers should be tested routinely for tumors in these sites in young patients. Optimal treatment strategy based on accurate diagnosis and comprehensive clinical assessment should be recommended.