Factors driving antimony accumulation in soil-pakchoi and wheat agroecosystems: Insights and predictive models.

The accumulation of antimony (Sb) in plants and its potential effects on human health are of increasing concern. Nevertheless, only a few countries or regions have established soil Sb thresholds for agricultural purposes, and soil properties have not been taken into account. This study investigated the accumulation of Sb in the edible parts of pakchoi and wheat grain by adding exogenous Sb to 21 soils with varying properties. The results revealed a positive correlation between bioavailable Sb (Sbava, extracted by 0.1 M K2HPO4) in soil and Sb in the edible parts of pakchoi (R2 = 0.77, p < 0.05) and wheat grain (R2 = 0.54, p < 0.05). Both machine learning and traditional multiple regression analysis indicated Sbava was the most critical feature and the main soil properties that contributed to Sb uptake by pakchoi and wheat were CaCO3 and clay, respectively. The advisory food limits for Sb in pakchoi and wheat were estimated based on health risk assessment, and used to derive soil thresholds for safe pakchoi and wheat production based on Sbtot and Sbava, respectively. These findings hold potential for predicting Sb uptake by crops with different soil properties and informing safe production management strategies.

Mitophagy in ototoxicity.

Mitochondrial dysfunction is associated with ototoxicity, which is caused by external factors. Mitophagy plays a key role in maintaining mitochondrial homeostasis and function and is regulated by a series of key mitophagy regulatory proteins and signaling pathways. The results of ototoxicity models indicate the importance of this process in the etiology of ototoxicity. A number of recent investigations of the control of cell fate by mitophagy have enhanced our understanding of the mechanisms by which mitophagy regulates ototoxicity and other hearing-related diseases, providing opportunities for targeting mitochondria to treat ototoxicity.

The successful application of pyrotinib in the treatment of primary trastuzumab-resistant HER-2-positive breast cancer with bilateral axillary lymph node metastasis: a case report.

Breast cancer patients with synchronous contralateral axillary lymph node metastasis (CAM) are very rare, and there is a lack of published treatment guidelines for this kind of patients. We presented a human epidermal growth factor receptor 2 (HER-2)-positive breast cancer case, who was diagnosed as CAM with primary trastuzumab resistance. In this case report, we describes a 47-year-old woman diagnosed with HER-2 positive breast cancer with regional lymph nodes metastasis. However, physical examination identified contralateral axillary lymph nodes, the auxiliary inspection did not assist in determining the nature of the right axillary lymph nodes, and there was no obvious mass in the right breast. Hence, we performed the core needle biopsy on the right axillary lymph node, which revealed the presence of metastatic breast adenocarcinoma. The patient received trastuzumab-based treatment, but this only afforded a progression-free survival of 5 months, owing to primary trastuzumab resistance. She was then successfully treated with pyrotinib, and the outcome was close to clinical complete response (CCR) with a progression-free survival of over 27 months thus far. This case report may help inform clinicians in the diagnosis of breast cancer with CAM and offer the treatment options in HER-2-positive metastasis breast cancer with primary trastuzumab resistance.

Inhibition of ZEB1-AS1 confers cisplatin sensitivity in breast cancer by promoting microRNA-129-5p-dependent ZEB1 downregulation.

BACKGROUND: Breast cancer is the leading cause of cancer-related mortality in women worldwide. Long non-coding RNAs (lncRNAs) are of critical importance in tumor drug resistance. Herein, this study aims to determine the roles of lncRNA ZEB1-AS1 in drug resistance of breast cancer involving microRNA-129-5p (miR-129-5p) and ZEB1. METHODS: Microarray-based gene expression profiling of breast cancer was conducted to identify the differentially expressed lncRNAs. ZEB1 expression was measured in adjacent and cancerous tissues. Next, MCF-7 and MDA-MB-231 cells were treated with a series of inhibitor, mimic or siRNA to clarify the roles of lncRNA ZEB1-AS1 and miR-129-5p in drug resistance of breast cancer. Then the target relationship of miR-129-5p with lncRNA ZEB1-AS1 and ZEB1 was verified. The expression patterns of miR-129-5p, lncRNA ZEB1-AS1, Bcl-2, MDR-1, ZEB1 and corresponding proteins were evaluated. Moreover, the apoptosis and drug resistance of MCF-7 cell were detected by CCK-8 and flow cytometry respectively. RESULTS: LncRNA ZEB1-AS1 was observed to be an upregulated lncRNA in breast cancer, and ZEB1 overexpression was noted in breast cancerous tissues. MiR-129-5p was revealed to specifically bind to both ZEB1 and lncRNA ZEB1-AS1. Moreover, the expression levels of ZEB1-AS1, ZEB1, Bcl-2, MDR-1, and corresponding proteins were decreased, but the expression of miR-129-5p was increased with transfection of miR-129-5p mimic and lncRNA ZEB1-AS1 siRNA. Besides, drug resistance to cisplatin was inhibited, and cell apoptosis was promoted in breast cancer after transfection of miR-129-5p mimic, lncRNA ZEB1-AS1 siRNA, and ZEB1 siRNA. CONCLUSION: In conclusion, the study provides evidence that lncRNA ZEB1-AS1 silencing protects against drug resistance in breast cancer by promoting miR-129-5p-dependent ZEB1 downregulation. It may serve as a novel therapeutic target in breast cancer treatment.

Treatment after Progression on Fulvestrant among Metastatic Breast Cancer Patients in Clinical Practice: a Multicenter, Retrospective Study.

Fulvestrant (Ful) is an effective and widely used agent for first- and second-line treatment of hormone receptor-positive, human epidermal growth factor receptor-2-negative (HR+/HER2-) metastatic breast cancer (MBC). However, there is no evidence of treatment after progression on Ful. Our study aimed to investigate the profile of daily practice regarding therapy after Ful. A consecutive series of 131 HR+, HER2- MBC patients who failed Ful 500 mg as first-line or second-line therapy from June 2014 to June 2017 in 6 institutions were included and analysed. Among 131 patients who failed Ful with similar baseline characteristics, 31 (23.7%) received endocrine therapy (ET), and 100 (76.3%) were treated with chemotherapy (CT). The most frequently applied CT regimen was capecitabine (32%), and the ET regimen was exemestane + everolimus (35.5%). Multivariate analysis showed that patients with bone-only metastasis were associated with lower CT use (OR = 7.97, 95% CI 1.51-41.84, P = 0.01). Among patients who received CT and ET as subsequent treatments, the median progression-free survival (PFS) was 7.5 months (95% CI 6.2-8.8) and 6.0 months (95% CI 4.1-7.9), respectively (p = 0.03). Among patients who were resistant to Ful (PFS < 6 months), the PFS on CT was significantly longer than that on ET (7.1 months vs 3.9 months, p = 0.024, HR = 0.5, 95% CI 0.26-0.97); however, among patients with a PFS ≥6 months on Ful, the efficacy of CT and ET was similar. Additionally, among patients with an older age, bone-only metastasis and ≥3 metastatic sites, no significant difference was observed between the CT and ET groups. Moreover, ET was much more tolerated than CT in terms of the incidence of grade 3/4 toxicities (9.6% vs 27%, P < 0.05). Median overall survival (OS) was not reached. Thus, our findings reveal the pattern of post-Ful treatment in current clinical practice and provide evidence on the efficacy, safety and choice of these treatments.

MicroRNA-590-5p functions as a tumor suppressor in breast cancer conferring inhibitory effects on cell migration, invasion, and epithelial-mesenchymal transition by downregulating the Wnt-ß-catenin signaling pathway.

Breast cancer remains one of the foremost primary causes of female morbidity and mortality worldwide. During the current study, the effect of miR-590-5p and paired-like homeodomain transcription factor 2 (PITX2) on proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) of human breast cancer via the Wnt-ß-catenin signaling pathway was investigated. Breast cancer-related genes and related signaling pathways were obtained from KEGG database. The PITX2 regulatory microRNA was predicted. To define the contributory role by which miR-590-5p influences the progression of breast cancer, the interaction between miR-590-5p and PITX2 was explored; the proliferation, invasion, and migration abilities as well as the tumor growth and metastasis in nude mice were detected following the overexpression or silencing of miR-590-5p. PITX2 was determined to share a correlation with breast cancer and miR-590-5p was selected for further analysis. PITX2, Wnt-1, ß-catenin, N-cadherin, and vimentin all displayed higher levels, while miR-590-5p and E-cadherin expression were lower among breast cancer tissues than in the adjacent normal tissue. After overexpression of miR-590-5p or si-PITX2, the expression of E-cadherin was markedly increased, decreases in the expression of Wnt-1, ß-catenin, N-cadherin, and vimentin, as well as inhibited cell proliferation, invasion, migration, metastasis, and EMT were observed. This study provides evidence suggesting that the transfection of overexpressed miR-590-5p can act to alleviate the effects of breast cancer demonstrating an ability to inhibit the processes of cell proliferation, migration, and invasion as well as EMT by suppressing the expression of PITX2 and activation of the Wnt-ß-catenin pathway.

TGF-beta 1 levels are associated with lymphocyte percentages in patients with lung cancer treated with radiation therapy.

PURPOSE: Plasma TGF-ß1 protein levels reportedly may predict the treatment outcomes of lung cancer. We hypothesized that in patients with lung cancer treated with radiation therapy (RT), TGF-ß1 levels may correlate with the percentages of CD4+ T cells, CD8+ T cells, and the CD4+/CD8+ T cell ratio in peripheral blood. PATIENTS AND METHODS: Eighty-two lung cancer patients satisfied the inclusion criteria. Platelet-poor plasma was obtained before RT, at the second and fourth weeks during RT, and at the end of RT (pre-, during-, and post-RT, respectively). TGF-ß1 was measured via ELISA, while recording the percentages of lymphocyte subsets in peripheral blood. Short-term efficacy was categorized as complete response, partial response, stable disease, or progressive disease. RESULTS: Patients who had significantly lower TGF-ß1 protein levels after RT than pre-RT seemed to have a better short-term effect (P<0.05) than those who had higher TGF-ß1 levels. There was a significant association between the TGF-ß1 levels and percentages of CD4+ T cells, CD8+ T cells, or CD4+/CD8+ T cell ratio during and at the end of RT. Changes in CD3+ T cells, B cells, or natural killer cells were not statistically related to the changes in TGF-ß1 levels. CONCLUSION: Lung cancer patients with TGF-ß1 levels in plasma after RT that are below pre-RT levels may experience better short-term efficacy. The underlying mechanism may be related to the influence of TGF-ß1 on antitumor immunity.

Downregulated GBX2 gene suppresses proliferation, invasion and angiogenesis of breast cancer cells through inhibiting the Wnt/ß-catenin signaling pathway.

OBJECTIVE: Gastrulation brain homeobox 2 (GBX2), a gene involved in mid/hindbrain region, has been revealed as one of the oncogene associated with certain cancers, as an example being prostate cancer. However, despite years of worldwide research, the underlying mechanism of GBX2 as well as its significance in breast cancer still remains unclear. Therefore, the present study evaluates the abilities of GBX gene silencing providing for the proliferation, invasion and angiogenesis of breast cancer cells by way of the Wnt/ß-catenin signaling pathway. METHODS: We employed a microarray analysis to screen out differentially expressed genes relative to breast cancer. Moreover, we retrieved GBX2 expression in breast cancer to find out the relationship between GBX2 expression and prognosis in breast cancer. We performed RT-qPCR to screen out cell lines with high GBX2 expression. Subsequently, both RT-qPCR and western blot analysis were employed so as to measure the combination of the mRNA and protein expressions of GBX2, ß-catenin, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, and MMP-9. The effect that GBX2 gene silencing and the Wnt/ß-catenin signaling pathway had on cell proliferation, invasion, angiogenesis, and tumorigenic ability were evaluated. RESULTS: GBX2 gene was also identified having played a role in breast cancer development due to its association with the Wnt/ß-catenin signaling pathway. GBX2 gene silencing was found to be an inhibitor for the mRNA and protein expressions regulating ß-catenin, VEGF, MMP-2, and MMP-9. Cell proliferation, invasion, angiogenesis, as well as tumorigenic ability in breast cancer were investigated and found to have been suppressed by the GBX2 gene silencing or inactivation of the Wnt/ß-catenin signaling pathway. CONCLUSION: The study has made an attempt to provide evidence to the idea that GBX2 gene silencing has an inhibition effect on the proliferation, invasion and angiogenesis of the breast cancer cells by inhibiting the activation of the Wnt/ß-catenin signaling pathway.

Correlation between polymorphisms of nicotine acetylcholine acceptor subunit CHRNA3 and lung cancer susceptibility.

Both environmental and genetic factors participate in the pathogenesis of lung cancer. The aim of this study was to explore the association between CHRNA3 polymorphisms of the nicotinic acetylcholine receptor gene and lung cancer risk in a hospital-based, case-controlled study. Single nucleotide polymorphisms (SNPs) in CHRNA3 rs3743073 (A>G) were determined using the TaqMan-MGB probe technique in 600 lung cancer cases and 600 normal controls. The differences in genotype and allele frequency were compared between groups and their association with lung cancer. The genotype frequency of rs3743073 (A>G) demonstrated Hardy-Weinberg equilibrium (P<0.05). The genotype and allele frequencies were significantly different between the cancer and control groups (P<0.05). Compared with patients with the TT genotype, lung cancer incidence was increased in patients with the TG and GG genotypes (OR=1.68; 95% CI, 1.30-2.19; P<0.05; OR=1.30; 95% CI, 1.05-1.61; P<0.05, respectively). Patients with rs3743073G variant alleles (TG and GG) were at greater risk (OR=0.65; 95% CI, 0.50-0.84; P<0.05) of developing lung cancer. Increased risk associated with rs3743073G variant alleles was observed in male smokers over the age of 60 (P<0.05). In this cohort, the CHRNA3 gene rs3743073G variant genotype significantly increased lung cancer risk, especially in male smokers over the age of 60.

Polymorphisms of the ribonucleotide reductase M1 gene and sensitivity to platin-based chemotherapy in non-small cell lung cancer.

Ribonucleotide reductase catalyzes the rate limiting step of deoxyribonucleotide formation, a crucially important step in DNA synthesis and repair. The regulatory subunit M1 of ribonucleotide reductase (RRM1) is the necessary part of the RR function and controls substrate specificity and global on/off enzyme activity. Despite recent research progress, the role of RRM1 in lung cancer sensitivity to chemotherapeutics remains to be elucidated. This study was to investigate the relationship between polymorphisms of the RRM1 gene and sensitivity to platinum-based chemotherapy in non-small cell lung cancer (NSCLC). Genomic DNA samples from 214 NSCLC patients treated with platinum-based chemotherapy were used to determine the RRM1 promoter allelotypes. The RR37CC-RR524TT was the most frequent allelotype (38.50%), followed by RR37AC-RR524CT (26.76%) and RR37CC-RR524CT (14.95%). The average response rate for chemotherapy was 44.4%. The response rates to the treatment regimens in the RR37CC-RR524TT, RR37AC-RR524CT and RR37CC-RR524CT allelotypes were 43.9%, 52.6%, and 51.6%, respectively. The response rates to therapy among patients with RRM1 (-)524 allelotypes were significantly different (p=0.046), whereas that among patients with RRM1 (-)37 allelotypes were not significant. Further analysis showed that the response rate in the patients with RR524CT allelotype (52.3%) was the highest, compared with that with RR37CC-RR524TT allelotype (43.9%, p=0.28), or the Others (RR524CC and RR37AC-RR524TT, 30.2%, p=0.02). Our results suggest that the RR524CT allelotype may be associated with an increased sensitivity to platinum-based chemotherapy in NSCLC. Further research on determining RR524CT as a clinical marker for predicting response to platinum-based therapy in NSCLC patients is warranted.