Comprehensive Transcriptomic and Proteomic Analyses Identify a Candidate Gene Set in Cross-Resistance for Endocrine Therapy in Breast Cancer.

Endocrine therapy (ET) of selective estrogen receptor modulators (SERMs), selective estrogen receptor downregulators (SERDs), and aromatase inhibitors (AIs) has been used as the gold standard treatment for hormone-receptor-positive (HR+) breast cancer. Despite its clinical benefits, approximately 30% of patients develop ET resistance, which remains a major clinical challenge in patients with HR+ breast cancer. The mechanisms of ET resistance mainly focus on mutations in the ER and related pathways; however, other targets still exist from ligand-independent ER reactivation. Moreover, mutations in the ER that confer resistance to SERMs or AIs seldom appear in SERDs. To date, little research has been conducted to identify a critical target that appears in both SERMs/SERDs and AIs. In this study, we conducted comprehensive transcriptomic and proteomic analyses from two cohorts of The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) to identify the critical targets for both SERMs/SERDs and AIs of ET resistance. From a treatment response cohort with treatment response for the initial ET regimen and an endocrine therapy cohort with survival outcomes, we identified candidate gene sets that appeared in both SERMs/SERDs and AIs of ET resistance. The candidate gene sets successfully differentiated progress/resistant groups (PD) from complete response groups (CR) and were significantly correlated with survival outcomes in both cohorts. In summary, this study provides valuable clinical implications for the critical roles played by candidate gene sets in the diagnosis, mechanism, and therapeutic strategy for both SERMs/SERDs and AIs of ET resistance for the future.

Seroepidemiology of Toxocara canis infection among primary schoolchildren in the capital area of the Republic of the Marshall Islands.

BACKGROUND: Toxocariasis, which is predominantly caused by Toxocara canis (T. canis) infection, is a common zoonotic parasitosis worldwide; however, the status of toxocariasis endemicity in the Republic of the Marshall Islands (RMI) remains unknown. METHODS: A seroepidemiological investigation was conducted among 166 primary school children (PSC) aged 7-12 years from the capital area of the RMI. Western blots based the excretory-secretory antigens of larval T. canis (TcES) was employed, and children were considered seropositive if their serum reacted with TcES when diluted at a titer of 1:64. Information regarding demographic characteristics of and environmental risk factors affecting these children was collected using a structured questionnaire. A logistic regression model was applied to conduct a multivariate analysis. RESULTS: The overall seropositive rate of T. canis infection was 86.75% (144/166). In the univariate analysis, PSC who exhibited a history of feeding dogs at home (OR = 5.52, 95% CI = 1.15-26.61, p = 0.02) and whose parents were employed as nonskilled workers (OR = 2.86, 95% CI = 1.08-7.60, p = 0.03) demonstrated a statistically elevated risk of contracting T. canis infections. Cleaning dog huts with gloves might prevent infection, but yielded nonsignificant effects. The multivariate analysis indicated that parental occupation was the critical risk factor in this study because its effect remained significant after adjusting for other variables; by contrast, the effect of dog feeding became nonsignificant because of other potential confounding factors. No associations were observed among gender, age, consuming raw meat or vegetables, drinking unboiled water, cleaning dog huts with gloves, or touching soil. CONCLUSIONS: This is the first serological investigation of T. canis infection among PSC in the RMI. The high seroprevalence indicates the commonness of T. canis transmission and possible human risk. The fundamental information that the present study provides regarding T. canis epidemiology can facilitate developing strategies for disease prevention and control.

SUV39H1 Expression as a Guideline for Omitting Radiotherapy in Lymph Node-positive Triple-negative Breast Cancer Patients.

BACKGROUND/AIM: The role of postoperative radiotherapy (RT) combined with chemotherapy (CT) for lymph node-positive (LN+) triple-negative breast cancer (TNBC) remains controversial. SUV39H1-mediated epigenetic regulation is associated with cancer cell migration, invasion, metastasis, and treatment resistance. This study aims to identify the role of SUV39H1 in TNBCs. MATERIALS AND METHODS: Overall, 498 TNBCs with SUV39H1 RNA-seq profiles were retrieved from TCGA-BRCA and analyzed; the X-tile algorithm was used to stratify the population into low, intermediate, and high SUV39H1. Furthermore, we performed an in vitro clonogenic cell survival assay using the MDA-MB-231 cell line to assess the effects of SUV39H1 on cellular responses. RESULTS: The results showed that SUV39H1 was significantly higher in TNBC than normal tissue and luminal subtype breast cancer. Notably, SUV39H1 is significantly expressed in the basal-like 1 (BL1) and immunomodulatory (IM) subgroups, compared to other subtypes. Compared to patients with a low or medium expression of SUV39H1, omitting RT only worsens disease-free survival (DFS) in those with high SUV39H1 expression. The experimental results showed SUV39H1 was suppressed by si-SUV39H1, and SUV39H1 knockdown in MDA-MB-231-IV2-1 cells enhanced the cellular toxicity of doxorubicin and paclitaxel. CONCLUSION: Targeting SUV39H1 may provide a potential guiding indication of omitting RT to avoid over-treatment and chemosensitivity for TNBC.

Toxoplasma gondii infection: seroprevalence and associated risk factors among primary school children in the capital area of the Republic of the Marshall Islands.

Although Toxoplasma gondii infection is commonly prevalent in the tropical/subtropical regions, the prevalence of toxoplasmosis in the Republic of the Marshall Islands (RMI) remains unclear. A seroepidemiological survey was undertaken for investigating T. gondii infection in primary school children (PSC) using the latex agglutination (LA) test in the capital area of RMI. Information on demographic characteristics and environmental risk factors was collected via a structured questionnaire. Logistic regression model was applied for multivariate analysis. The overall infection rate of T. gondii was found to be 54.8%. Significant gender differences were found at different urbanization levels. PSC with LA titers of ≥ 1:1,024, indicating high responders, were found to be younger age group than others (8.7 years vs. 10.3 years, P = 0.003); moreover, infection rates among both age groups as well as high responders showed a decreasing trend with age. Multivariate analysis revealed that residing in urban rather than suburban settings was associated with increased risk of infection (P = 0.04). No associations were found between raw meat consumption, drinking unboiled water, and cleaning of cat hutch using gloves. This is the first serological survey of T. gondii infection among PSC in RMI and could help in the development of strategies in the future for disease prevention and control of T. gondii transmission.