Background/Aim: The anti-cancer effect of high doses of intravenous vitamin C (high-dose vitamin C) remains controversial despite growing evidence that high-dose vitamin C exerts anti-tumorigenic activity by increasing the amount of reactive oxygen species in cancer cells without meaningful toxicities. Therefore, this study attempted to demonstrate the in vitro anti-cancer activity of high-dose vitamin C in combination with conventional treatment in breast cancer. Materials and Methods: The pro-apoptotic effects of high-dose vitamin C (1.25 to 20 mM) with or without anti-cancer agents (eribulin mesylate, tamoxifen, fulvestrant, or trastuzumab) were estimated using an MTT assay to measure the cell viability of a variety of breast cancer cell lines (MCF7, SK-BR3, and MDA-MB-231), as well as normal breast epithelial cells (MCF10A). Results: High-dose vitamin C (≥10 mM) significantly decreased cell viability of all breast cancer cell lines, particularly of MCF-7 cells. The catalase activities of MCF7 and MDA-MD-231 cells were also lower than those of MCF10A cells. Moreover, cell viability of both MCF7 and MDA-MD-231 cells was decreased further when combining high-dose vitamin C and eribulin mesylate, and this was also true for MCF-7 cells when combining high-dose vitamin C with tamoxifen or fulvestrant and for SK-BR3 cells when combining high-dose vitamin C with trastuzumab in comparison with chemotherapy or endocrine therapy alone. Conclusion: Combining high-dose vitamin C with conventional anti-cancer drugs can have therapeutic advantages against breast cancer cells.

Objectives: The clinical significance of aquaporin-1 (AQP1), aquaporin-3 (AQP3), and aquaporin-5 (AQP5) expression was analyzed in a large number of patients with colon cancer. Methods: AQP1, AQP3, and AQP5 expression was investigated based on the immunohistochemistry of tissue microarray specimens from 486 colon cancer patients who underwent curative surgery. Scores were given to the staining intensity and percentage of positive cells, and the staining score was defined as the sum of these scores then used to categorize the AQP expression as negative, weakly AQP-positive, or strongly AQP-positive. Results: A total of 298 (61.3%) patients were identified as strongly AQP1-positive (staining score ≥6), while 38 (7.8%) were strongly AQP3-positive and 145 (29.8%) were strongly AQP5-positive. The overexpression of AQP1, AQP3, and AQP5 was significantly correlated with lymph node metastasis in a multivariate logistic analysis (AQP1, p = 0.026; AQP3, p = 0.023; AQP5, p = 0.003). While the multivariate survival analysis, which included age, histology, TNM stage, and CEA level showed that the expression of AQP1, AQP3, and AQP5 had no effect on the overall survival and disease-free survival. Conclusions: The current study found a significant correlation between AQP1, AQP3, and AQP5 expression and lymph node metastasis in patients with surgically resected colon cancer.

Purpose: To evaluate a triplet regimen combining immune checkpoint blockade, AKT pathway inhibition, and (nab-) paclitaxel as first-line therapy for locally advanced/metastatic triple-negative breast cancer (mTNBC). Patients and Methods: The single-arm CO40151 phase Ib study (NCT03800836), the single-arm signal-seeking cohort of IPATunity130 (NCT03337724), and the randomized phase III IPATunity170 trial (NCT04177108) enrolled patients with previously untreated mTNBC. Triplet therapy comprised intravenous atezolizumab 840 mg (days 1 and 15), oral ipatasertib 400 mg/day (days 1–21), and intravenous paclitaxel 80 mg/m2 (or nab-paclitaxel 100 mg/m2; days 1, 8, and 15) every 28 days. Exploratory translational research aimed to elucidate mechanisms and molecular markers of sensitivity and resistance. Results: Among 317 patients treated with the triplet, efficacy ranged across studies as follows: median progression-free survival (PFS) 5.4 to 7.4 months, objective response rate 44% to 63%, median duration of response 5.6 to 11.1 months, and median overall survival 15.7 to 28.3 months. The safety profile was consistent with the known toxicities of each agent. Grade ≥3 adverse events were more frequent with the triplet than with doublets or single-agent paclitaxel. Patients with PFS >10 months were characterized by NF1, CCND3, and PIK3CA alterations and increased immune pathway activity. PFS <5 months was associated with CDKN2A/CDKN2B/MTAP alterations and lower predicted phosphorylated AKT-S473 levels. Conclusions: In patients with mTNBC receiving an ipatasertib/atezolizumab/taxane triplet regimen, molecular characteristics may identify those with particularly favorable or unfavorable outcomes, potentially guiding future research efforts.

Aim: We evaluated the role of long noncoding ribonucleic acid (lncRNA) in breast cancer cell lines by quantitative reverse transcription-polymerase change reaction. Materials and Methods: The effects of small NF90-associated RNA (snaR) with RNA interference on proliferation, migration and invasion of MDA-MB-231 cells were observed by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide, wound healing and transwell assay. Results: Among 90 lncRNAs, E2F transcription factor 4, p107/p130-binding (E2F4) antisense, insulin-like growth factor 2 antisense (IGF2AS), snaR, and small nucleolar RNA host gene 5 (SNHG5) were up-regulated in MDA-MB-231 and 7SK, antisense noncoding RNA in the INK4 locus (ANRIL), IGF2AS, Nespas, p53 mRNA, and snaR were up-regulated in MCF-7 cells. Down-regulation of snaR inhibited the proliferation, migration, and invasion of MDA-MD-231 breast cancer cells. Conclusion: LncRNA snaR was found to be up-regulated in breast cancer cells, and the cancer progression of MDA-MB-231 cells was significantly suppressed by down-regulation of snaR. Therefore, snaR knockdown has potential as a treatment modality for triple-negative breast cancer.

MicroRNAs (miRNAs) can be used to target a variety of human malignancy by targeting their oncogenes or tumor suppressor genes. The developmental endothelial locus-1 (Del-1) might be under miRNA regulation. This study investigated microRNA-137 (miR-137) function and Del-1 expression in triple-negative breast cancer (TNBC) cells and tissues. Del-1 mRNA and miRNA-137 levels were determined via qRT-PCR in breast cancer cells (MDA-MB-231, MCF7, SK-BR3, and T-47D) and tissues from 30 patients with TNBC. The effects of miR-137 on cell proliferation, migration, and invasion were determined using MTT assays, wound healing, and Matrigel transwell assays. The luciferase reporter assay revealed direct binding of miR-137 to the 3′-UTR of Del-1. miR-137 inhibited cell proliferation, migration, and invasion of MDA-MB-231 cells. Among the 30 TNBC specimens, miR-137 was downregulated and Del-1 level in plasma was significantly elevated relative to normal controls. It is concluded that miR-137 regulates Del-1 expression in TNBC by directly binding to the Del-1 gene and cancer progression. The results implicate miR-137 as a new therapeutic biomarker for patients with TNBC.