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Background: Clinical trials have demonstrated that the 21-gene assay (Oncotype DX) can predict the benefits of adjuvant chemotherapy in patients with hormone receptor-positive (HR+) and human epidermal growth factor 2-negative (HER2−) breast cancer. This study investigated the real-world utilization of this genomic test in Taiwanese patients. Materials and Methods: We compiled data on the recurrence score (RS) and clinicopathological characteristics of patients who received the 21-gene assay between August 2016 and August 2021. Survival outcomes were analyzed using the Kaplan–Meier method and log-rank test. Correlations between clinicopathological characteristics and RSs were analyzed using the Chi-square test or Fisher's exact test. Results: Of the 106 recruited patients, 34 and 72 were classified into different risk groups using conventional and Trial Assigning Individualized Options for Treatment (TAILORx)-based cutoff points, respectively. In the conventional stratification group, 61.8%, 29.4%, and 8.8% of the patients were classified into the low-risk (RS: 0–17), intermediate-risk (RS: 18–30), and high-risk (RS: 31–100) categories, respectively. In the TAILORx stratification group, 18.1%, 72.2%, and 9.7% of the patients were classified into the low-risk (RS: 0–10), intermediate-risk (RS: 11–25), and high-risk (RS: 26–100) categories, respectively. In survival analysis, recurrence-free survival did not significantly differ among discrete risk categories. The high-risk category determined using TAILORx-based cutoff points was associated with the presence of >14% Ki-67-positive cells (P = 0.004) and tumor histology Grade III (P = 0.001). Conclusion: Using the Oncotype DX assay, we classified a small proportion of our Taiwanese patients into the high-risk category; no survival difference was observed among the patients in distinct risk categories. These results suggest the clinical utility of the 21-gene assay in Taiwanese patients with early HR+/HER2−breast cancer. [ABSTRACT FROM AUTHOR]

Aim: To assess the outcomes of metabolic surgery in overweight and obese patients in Asia with type 2 diabetes (T2D). Materials and Methods: The treatment outcomes of 1999 patients from the Asian Diabetes Surgery Summit database were analysed. The changes in treatment effects across time were assessed with respect to the surgical procedures performed by using generalized estimating equations. Results: The most commonly performed procedure was the single‐anastomosis gastric bypass (32.6%). Weight (from 106.2 ± 25.1 to 77.9 ± 18.8 kg), body mass index (BMI; from 38.7 ± 7.9 to 28.5 ± 5.9 kg/m2), blood sugar (from 9.3 ± 4.1 to 5.7 ± 1.8 mmol/L) and HbA1c (from 8.4% ± 1.8% to 6.0% ± 1.1%) significantly improved from baseline to 1 year (P <.001) and remained stable at 5 years (weight, 86.3 ± 23.3 kg; BMI, 31.7 ± 7.9 kg/m2; blood sugar, 5.8 ± 1.8 mmol/L, and HbA1c, 6.4% ± 1.2%; all P <.001 vs. baseline). Blood pressure and most lipid disorders also improved significantly. Of the treatment procedures, single‐anastomosis gastric bypass had the most satisfactory outcomes with statistical significance for most disorders, whereas adjustable gastric banding displayed the least satisfactory outcomes. Conclusions: Metabolic surgery remarkably improved body weight, T2D and other metabolic disorders in Asian patients. However, the efficacy of individual procedures varied substantially. [ABSTRACT FROM AUTHOR]

Germline pathogenic mutation of the BRCA gene increases the prevalence of breast cancer. Reports on the benign variants of BRCA genes are limited. However, the definition of these variants might be altered with the accumulation of clinical evidence. Therefore, in the present study, we focused on benign single nucleotide polymorphisms (SNPs) of BRCA genes. Linkage disequilibrium was calculated from whole genome sequencing of the BRCA genes obtained from 500 healthy controls and 49 breast cancer patients. Sanger sequencing was used to confirm the mutation. The linkage disequilibrium was noted for seven and three SNPs in the BRCA1 and BRCA2 genes, respectively. Breast cancer with BRCA1/2 linkage disequilibrium was not correlated with a personal history of benign diseases or family history of cancer. Nevertheless, breast cancer with BRCA1 linkage disequilibrium was correlated with high tumor-infiltrating lymphocytes and positive extensive intraductal components. The patients with BRCA1 linkage disequilibrium tended to have worse disease-specific survival. Cancers with BRCA2 linkage disequilibrium are associated with a lower ratio of grade III cancer. Moreover, patients with BRCA2 linkage disequilibrium tended to have better overall survival. In conclusion, linkage disequilibrium from benign SNPs of the BRCA genes potentially affects cancer characteristics., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Metabolic surgery is recognized for its effectiveness in weight loss and improving outcomes for individuals with type 2 diabetes mellitus (T2DM). However, its impact on renal function, especially in multi-ethnic Asian populations, remains underexplored. This study investigates mid- and long-term renal outcomes following metabolic surgery in Asian patients with T2DM., Methods: This retrospective cohort study utilized data from the Asian Diabetes Surgery Study (ADSS), involving T2DM patients aged 20-79 who underwent metabolic surgery from 2008 to 2015. The primary outcome was the change in estimated glomerular filtration rate (eGFR) at 1, 3, and 5 years post-surgery, with adjustments for confounders. Secondary outcomes included changes in chronic kidney disease (CKD) stages and the relationship between weight loss and eGFR changes. Data were analyzed using univariate and multivariable regression analyses, along with the McNemar test., Results: The study included 1513 patients with a mean age of 42.7 years. The results revealed that a significant improvement in eGFR was observed at 1-year post-surgery (112.4 ± 32.0 ml/min/1.73 m², P  < .001), with a shift toward less severe CKD stages. However, this improvement was not sustained at 3 and 5 years. No significant correlation was found between weight loss and eGFR changes at 1-year follow-up., Conclusion: Metabolic surgery significantly improves renal function at 1 year postoperatively in Asian individuals with T2DM, highlighting its potential benefits beyond glycemic control and weight loss. The long-term effects on renal function require further investigation., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Tumor progression is dependent on tumor cells and their microenvironment. It is important to identify therapies that inhibit cancer cells and activate immune cells. Arginine modulation plays a dual role in cancer therapy. Arginase inhibition induced an anti-tumor effect via T-cell activation through an increase in arginine in the tumor environment. In contrast, arginine depletion by arginine deiminase pegylated with 20,000-molecular-weight polyethylene glycol (ADI-PEG 20) induced an anti-tumor response in argininosuccinate synthase 1 (ASS1)-deficient tumor cells. ADI-PEG 20 did not cause toxicity to normal immune cells, which can recycle the ADI-degraded product citrulline back to arginine. To target tumor cells and their neighboring immune cells, we hypothesized that the combination of an arginase inhibitor (L-Norvaline) and ADI-PEG 20 may trigger a stronger anticancer response. In this study, we found that L-Norvaline inhibits tumor growth in vivo. Pathway analysis based on RNA-seq data indicated that the differentially expressed genes (DEGs) were significantly enriched in some immune-related pathways. Significantly, L-Norvaline did not inhibit tumor growth in immunodeficient mice. In addition, combination treatment with L-Norvaline and ADI-PEG 20 induced a more robust anti-tumor response against B16F10 melanoma. Furthermore, single-cell RNA-seq data demonstrated that the combination therapy increased tumor-infiltrating CD8 + T cells and CCR7 + dendritic cells. The increase in infiltrated dendritic cells may enhance the anti-tumor response of CD8 + cytotoxic T cells, indicating a potential mechanism for the observed anti-tumor effect of the combination treatment. In addition, populations of immunosuppressive-like immune cells, such as S100a8 + S100a9 + monocytes and Retnla + Retnlg + TAMs, in tumors were dramatically decreased. Importantly, mechanistic analysis indicated that the processes of the cell cycle, ribonucleoprotein complex biogenesis, and ribosome biogenesis were upregulated after combination treatment. This study implied the possibility of L-Norvaline as a modulator of the immune response in cancer and provided a new potential therapy combined with ADI-PEG 20., Competing Interests: None., (AJCR Copyright © 2023.)

The incidence of breast cancer is increasing, and is one of the leading causes of cancer death worldwide. Dysregulation of NOTCH1 signaling is reported in breast cancer. In present study, bioinformatics was utilized to study the expression of NOTCH1 gene in breast cancer from public databases, including the Kaplan-Meier Plotter, PrognoScan, Human Protein Atlas, and cBioPortal. The relationship between NOTCH1 mRNA expression and survival of patients was inconsistent in public databases. In addition, we performed immunohistochemistry (IHC) staining of 135 specimens from our hospital. Lower cytoplasmic staining of NOTCH1 protein was correlated with cancer recurrence, bone metastasis, and a worse disease-free survival of patients, especially those with estrogen receptor-positive and human epidermal growth factor receptor 2-positive (HER2 + ) cancers. In TCGA breast cancer dataset, lower expression of NOTCH1 in breast cancer specimens was correlated with higher level of CCND1 (protein: cyclin D1). Decreased expression of NOTCH1 was correlated with lower level of CCNA1 (protein: cyclin A1), CCND2 (protein: cyclin D2), CCNE1 (protein: cyclin E1), CDK6 (protein: CDK6), and CDKN2C (protein: p18). In conclusion, NOTCH1 mRNA expression is not consistently correlated with clinical outcomes of breast cancer patients. Low cytoplasmic expression of NOTCH1 in IHC study is correlated with poor prognosis of breast cancer patients. Cytoplasmic localization of NOTCH1 protein failed to initial oncogenic signaling in present study. Expression of NOTCH1 mRNA was discordant with cell cycle-related genes. Regulation of NOTCH1 in breast cancer involves gene expression, protein localization and downstream signaling., Competing Interests: None., (AJCR Copyright © 2022.)