The Impact of Various Organic Phosphorus Carriers on the Uptake and Use Efficiency in Barley.

Organic phosphorus (OP) is an essential component of the soil P cycle, which contributes to barley nutrition after its mineralization into inorganic phosphorus (Pi). However, the dynamics of OP utilization in the barley rhizosphere remain unclear. In this study, phytin was screened out from six OP carriers, which could reflect the difference in OP utilization between a P-inefficient genotype Baudin and a P-efficient genotype CN4027. The phosphorus utilization efficiency (PUE), root morphological traits, and expression of genes associated with P utilization were assessed under P deficiency or phytin treatments. P deficiency resulted in a greater root surface area and thicker roots. In barley fed with phytin as a P carrier, the APase activities of CN4027 were 2-3-fold lower than those of Baudin, while the phytase activities of CN4027 were 2-3-fold higher than those of Baudin. The PUE in CN4027 was mainly enhanced by activating phytase to improve the root absorption and utilization of Pi resulting from OP mineralization, while the PUE in Baudin was mainly enhanced by activating APase to improve the shoot reuse capacity. A phosphate transporter gene HvPHT1;8 regulated P transport from the roots to the shoots, while a purple acid phosphatase (PAP) family gene HvPAPhy_b contributed to the reuse of P in barley.

Efficacy comparisons of solvent-based paclitaxel, liposomal paclitaxel, nanoparticle albumin-bound paclitaxel, and docetaxel after neoadjuvant systemic treatment in breast cancer.

PURPOSE: There are four kinds of taxanes: solvent-based paclitaxel (Sb-P), liposomal paclitaxel (Lps-P), nanoparticle albumin-bound paclitaxel (Nab-P), and docetaxel. This study aims to retrospectively evaluate the efficacy of different taxanes on neoadjuvant systemic treatment (NST) in breast cancer. METHODS: Patients who were diagnosed with breast cancer and had received integral NST from August 2013 to April 2022 were enrolled. The efficacy was divided into total pathological complete response (total-pCR), breast pathological complete response (breast-pCR), and axillary pathological complete response (axillary-pCR) for in-depth analysis and discussion. RESULTS: The choice of taxane was an independent risk factor for total-pCR and breast-pCR rates. The highest total-pCR and breast-pCR rates were found in the Nab-P group. The difference was not significant among all the taxanes in the axillary-pCR rate. CONCLUSION: Nab-P significantly improved the total-pCR and breast-pCR rates. It should be the first choice among taxanes in NST for breast cancer.

QTL Mapping of Agronomic and Physiological Traits at the Seedling and Maturity Stages under Different Nitrogen Treatments in Barley.

Nitrogen (N) stress seriously constrains barley (Hordeum vulgare L.) production globally by influencing its growth and development. In this study, we used a recombinant inbred line (RIL) population of 121 crosses between the variety Baudin and the wild barley accession CN4027 to detect QTL for 27 traits at the seedling stage in hydroponic culture trials and 12 traits at the maturity stage in field trials both under two N treatments, aiming to uncover favorable alleles for N tolerance in wild barley. In total, eight stable QTL and seven QTL clusters were detected. Among them, the stable QTL Qtgw.sau-2H located in a 0.46 cM interval on the chromosome arm 2HL was a novel QTL specific for low N. Notably, Clusters C4 and C7 contained QTL for traits at both the seedling and maturity stages. In addition, four stable QTLs in Cluster C4 were identified. Furthermore, a gene (HORVU2Hr1G080990.1) related to grain protein in the interval of Qtgw.sau-2H was predicted. Correlation analysis and QTL mapping showed that different N treatments significantly affected agronomic and physiological traits at the seedling and maturity stages. These results provide valuable information for understanding N tolerance as well as breeding and utilizing the loci of interest in barley.

Nanoparticle albumin-bound paclitaxel-based neoadjuvant regimen: A promising treatment option for HER2-low-positive breast cancer.

This study aimed to compare the efficacy of neoadjuvant systemic therapy (NST) with solvent-based paclitaxel (Sb-P), liposomal paclitaxel (Lps-P), nanoparticle albumin-bound paclitaxel (Nab-P), and docetaxel in human epidermal growth factor receptor 2 (HER2)-low-positive and HER2-zero breast cancers. A total of 430 patients receiving 2-weekly dose-dense epirubicin and cyclophosphamide (EC) followed by 2-weekly paclitaxel (Sb-P, Lps-P, or Nab-P), or 3-weekly EC followed by 3-weekly docetaxel for NST were enrolled in the study. In HER2-low-positive patients, the pathological complete response (pCR) rate in Nab-P group was significantly higher than that in the other three paclitaxel groups (2.8 % in Sb-P group, 4.7 % in Lps-P group, 23.2 % in Nab-P group and 3.2 % in docetaxel group, p < 0.001). In HER2-zero patients, the pCR rate did not differ significantly among the four paclitaxel groups (p = 0.278). The NST regimen containing Nab-P could be considered a promising treatment option in HER2-low-positive breast cancer.

Prognostic analysis of three forms of Ki-67 in patients with breast cancer with non-pathological complete response before and after neoadjuvant systemic treatment.

BACKGROUND: Patients who do not achieve a pathological complete response (pCR) after neoadjuvant systemic treatment (NST) have a significantly worse prognosis. A reliable predictor of prognosis is required to further subdivide non-pCR patients. To date, the prognostic role in terms of disease-free survival (DFS) between the terminal index of Ki-67 after surgery (Ki-67T ) and the combination of the baseline Ki-67 at biopsy before NST (Ki-67B ) and the percentage change in Ki-67 before and after NST (Ki-67C ) has not been compared. AIM: This study aimed to explore the most useful form or combination of Ki-67 that can provide prognostic information to non-pCR patients. PATIENTS AND METHODS: We retrospectively reviewed 499 patients who were diagnosed with inoperable breast cancer between August 2013 and December 2020 and received NST with anthracycline plus taxane. RESULTS: Among all the patients, 335 did not achieve pCR (with a follow-up period of ≥1 year). The median follow-up duration was 36 months. The optimal cutoff value of Ki-67C to predict a DFS was 30%. A significantly worse DFS was observed in patients with a low Ki-67C (p < 0.001). In addition, the exploratory subgroup analysis showed relatively good internal consistency. Ki-67C and Ki-67T were considered as independent risk factors for DFS (both p < 0.001). The forecasting model combining Ki-67B and Ki-67C showed a significantly higher area under the curve at years 3 and 5 than Ki-67T (p = 0.029 and p = 0.022, respectively). CONCLUSIONS: Ki-67C and Ki-67T were good independent predictors of DFS, whereas Ki-67B was a slightly inferior predictor. The combination of Ki-67B and Ki-67C is superior to Ki-67T for predicting DFS, especially at longer follow-ups. Regarding clinical application, this combination could be used as a novel indicator for predicting DFS to more clearly identify high-risk patients.

Volume change rate before and after neoadjuvant systemic therapy of breast cancer is an efficacious evaluation index to predict pathological complete response.

Neoadjuvant systemic therapy (NST) is widely applied in breast cancer treatment, but individuals respond differently to the same NST regimen. It is unclear which patients should adjust their NST regimen and what such an adjustment should be, especially for patients with radiologically partial response (PR). This study aimed to identify a quantitative efficacy evaluation index to evaluate the therapeutic effect of NST. 164 patients were enrolled in this study received four cycles of epirubicin and cyclophosphamide (EC), followed by four cycles of taxanes with trastuzumab [T(H)], if needed. Of patients with a volume change rate of EC treatment (δV1) below 0.80, more than half benefited from subsequent T(H) treatment compared with EC treatment. Importantly, for δV1 of 0.80 and higher, patients' subsequent T(H) treatment was not as efficient as previous EC treatment and they have a lower pathological complete response (pCR) rate. Across all patients, nanoparticle albumin-bound paclitaxel had a numerically higher pCR rate over other taxanes in patients with triple-negative breast cancer. This study showed that the volume change rate is better than the diameter change rate in monitoring the therapeutic effect of NST. Furthermore, δV1 is a good quantitative efficacy evaluation index to distinguish patients resistant to EC treatment and predict the pCR rate and guide the adjustment of individualized NST regimens.

Comparison of clinicopathological characteristics and response to neoadjuvant systemic therapy in patients with HER2-low-positive and HER2-zero breast cancer.

Previous studies have observed that human epidermal growth factor receptor 2 (HER2)-low-positive patients and HER2-zero patients have different prognoses. This study was conducted to investigate whether there are differences in clinicopathological characteristics and the response to neoadjuvant systemic therapy (NST) defined as systemic treatment prior to surgery between HER2-low-positive patients and HER2-zero patients. We retrospectively analyzed the data of patients with HER2-negative breast cancer who received NST at the First Affiliated Hospital of Nanjing Medical University from 2014 to 2021. There were 238 patients with HER2-low-positive status and 198 patients with HER2-zero status. The proportion of hormone receptor (HR)-positive patients in the HER2-low-positive group was significantly higher than that in the HER2-zero group (82.8% vs 52.0%, p < 0.001). The HER2-low-positive group had more patients with low Ki67 expression (23.9% vs 16.2%, p = 0.045), higher mastectomy rate (94.5% vs 88.9%, p = 0.031), and larger pathological tumor size (21.6 vs 17.8 mm, p = 0.028) than the HER2-zero group. However, no significant differences were found in pathologic complete response (pCR) rates between the two groups. We draw a conclusion that patients with HER2-low status and HER2-zero status were not found to have different pCR rates after NST, irrespective of HR status. However, differences were observed in some clinicopathological characteristics between the two groups.

A prospective, randomized clinical trial of emergency treatment of chemotherapy-induced neutropenia and febrile neutropenia by pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF).

AIMS: As one of the mainstays of breast cancer therapy, chemotherapy inevitably induces neutropenia. In this study, we explored the role of PEG-rhG-CSF (pegylated recombinant human granulocyte colony-stimulating factor) in the emergency treatment of chemotherapy-induced grades 3-4 neutropenia. METHODS: A total of 100 patients with breast cancer were randomized (1:1) into the study. Fifty patients randomized to the experimental group were treated with PEG-rhG-CSF after grades 3-4 neutropenia following the first cycle of chemotherapy, while 50 patients randomized to the control group received a daily injection of rhG-CSF (recombinant human granulocyte colony-stimulating factor). The primary endpoint was the recovery time of grades 3-4 neutropenia. RESULTS: Compared with patients in the control group, the mean ± SD recovery time of grades 3-4 neutropenia and febrile neutropenia (FN) was significantly shorter for patients in the experimental group (grades 3-4, P = .000; grade 4, P = .000; FN, P = .038). There is no significant difference in the incidence of FN for the two groups. In the experimental group, the duration of grades 3-4 neutropenia in patients aged <60 years and ≥60 years was 2.15 and 3.20 days, respectively (P = .037). Adverse events (AEs) of any grade were reported in 37 (75.5%) and 28 (59.6%) patients from the two groups, respectively. No grade ≥3 AEs were reported. CONCLUSION: This study supported that the PEG-rhG-CSF was more effective and convenient than rhG-CSF for treating grades 3-4 neutropenia and FN in patients with breast cancer and had manageable toxicity.

A novel nomogram containing efficacy indicators to predict axillary pathologic complete response after neoadjuvant systemic therapy in breast cancer.

Background: Neoadjuvant systemic therapy (NST) could make some clinically node-positive (cN+) breast cancer patients achieve axillary pathologic complete response (pCR). This study aimed to identify the patients who are likely to achieve axillary pCR and help surgeons make surgical decisions on the axilla. Methods: The cN+ breast cancer patients who received NST from 2015 to 2021 at The First Affiliated Hospital of Nanjing Medical University were enrolled. Univariate and multivariate logistic regression analyses were performed, and a nomogram was constructed based on the results of multivariate logistic regression analysis to predict the probability of axillary pCR and validated. Results: The axillary pCR was achieved in 208 (38.7%) patients. Patients who had a higher radiological response rate of breast tumor (P = 0.039), smaller longest diameter of positive node after NST (P = 0.028), ER-negative status (P = 0.006), HER2-positive status (P = 0.048) and breast pCR (P < 0.001) were more likely to achieve axillary pCR. The nomogram had an area under the receiver operating characteristic curve (AUC) of 0.795 (95% CI: 0.747-0.843), and the calibration curve showed good agreement. Conclusion: A nomogram was constructed to predict the axillary pCR of cN+ patients receiving NST based on baseline and efficacy indicators to assist surgeons in making surgical decisions on the axilla.

Nomogram for predicting overall survival in patients with triple-negative apocrine breast cancer: Surveillance, epidemiology, and end results-based analysis.

PURPOSE: Triple-negative apocrine carcinoma (TNAC) is a sort of triple-negative breast cancer (TNBC) that is rare and prognosis of these patients is unclear. The present study constructed an effective nomogram to assist in predicting TNAC patients overall survival (OS). METHODS: A total of 373 TNAC patients from the surveillance, epidemiology, and end results (SEER) got extracted from 2010 to 2016 and were divided into training (n = 261) and external validation (n = 112) groups (split ratio, 7:3) randomly. A Cox regression model was utilized to creating a nomogram according to the risk factors affecting prognosis. The predictive capability of the nomogram was estimated with receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). RESULTS: Multivariate Cox regression analysis revealed age, surgery, chemotherapy, stage, and first malignant primary as independent predictors of OS. A prediction model was constructed and virtualized using the nomogram. The time-dependent area under the curve (AUC) showed satisfactory discrimination of the nomogram. Good consistency was shown on the calibration curves in OS between actual observations and the nomogram prediction. What's more, DCA showed that the nomogram had incredible clinical utility. Through separating the patients into groups of low and high risk group that connects with the risk system that shows a huge difference between the low-risk and high risk OS (P < 0.001). CONCLUSION: To predict the OS in TNAC patients, the nomogram utilizing the risk stratification system that is corresponding. These tools may help to evaluate patient prognosis and guide treatment decisions.

Nanoparticle albumin-bound paclitaxel is superior to liposomal paclitaxel in the neoadjuvant treatment of breast cancer.

Aim: The present study aimed to retrospectively compare the efficacy and safety between liposomal paclitaxel (Lps-P) and nanoparticle albumin-bound paclitaxel (Nab-P) in neoadjuvant systemic treatment (NST) of breast cancer. Materials & methods: Two hundred thirty-five patients who were diagnosed with invasive breast cancer and then received dose-dense NST with epirubicin and cyclophosphamide followed by paclitaxel were enrolled. Results: Nab-P has an advantage in improving the total and axillary-only pathologic complete response rate over Lps-P. Although Nab-P can cause a higher incidence and severity of peripheral sensory neuropathy (PSN), most symptoms are temporary and reversible. In the Lps-P group, the proportion of patients with residual irreversible PSN is larger. Conclusion: Nab-P might be superior to Lps-P in NST of breast cancer.

Neoadjuvant systemic treatment (NST) is recommended for many patients with breast cancer before they undergo surgery to remove the cancer. This study retrospectively compared the efficacy and safety of two potential NST drugs, liposomal paclitaxel (Lps-P) and nanoparticle albumin-bound paclitaxel (Nab-P). Two hundred thirty-five patients participated in the study. These patients had been diagnosed with invasive breast cancer and were recommended NST with paclitaxel before surgery. The results showed that more participants who received Nab-P had no signs of cancer in their tissue samples from their breasts and armpit lymph nodes than participants who received Lps-P. Although Nab-P can cause a higher incidence and severity of peripheral sensory neuropathy (PSN), most symptoms are temporary and reversible. In conclusion, Nab-P might be superior to Lps-P for NST.

Corrigendum: A novel nomogram containing efficacy indicators to predict axillary pathologic complete response after neoadjuvant systemic therapy in breast cancer.

[This corrects the article DOI: 10.3389/fendo.2022.1042394.].

The transcribed ultraconserved element uc.51 promotes the proliferation and metastasis of breast cancer by stabilizing NONO.

Long noncoding RNAs have recently emerged as significant contributors to cancers, including breast cancer (BC). One class of long noncoding RNAs called transcribed ultraconserved regions (T-UCRs) is highly conserved in many species and closely related to diverse physiological and pathological processes. However, the function of T-UCRs in BC remains largely unclear. In this study, we identified uc.51, a T-UCR that is overexpressed in both BC tissues and cell lines and is correlated with larger tumor size. Loss- and gain-of-function assays were performed in vitro and demonstrated that uc.51 promotes the proliferation, migration, and invasion of BC cells. Mechanistically, non-POU domain-containing octamer-binding protein (NONO) was found to physically interact with uc.51 by RNA pulldown followed by mass spectrometry. This interaction was further verified by RNA immunoprecipitation. Moreover, uc.51 positively regulated the expression of NONO, maintained its stability through the ubiquitin-proteasome system, and activated the phosphorylation of CREB. Rescue experiments demonstrated that NONO overexpression compensated for the attenuated influence on BC progression resulting from downregulation of uc.51, indicating that NONO functions downstream of uc.51. In vivo functional experiments also revealed a positive correlation between uc.51 expression and tumor size. Ki-67 and NONO levels in the lv-uc.51-shRNA group were decreased compared with those in the lv-con-shRNA group, according to the immunohistochemical staining results, and a decreased incidence of distant metastasis was observed in the lv-uc.51-shRNA group in the xenograft model. Collectively, our results reveal a substantial role for the uc.51-NONO axis in BC progression and indicate that the uc.51-NONO axis has potential to be a therapeutic target for BC.

Can axillary surgery be omitted in patients with breast pathologic complete response after neoadjuvant systemic therapy for breast cancer? A real-world retrospective study in China.

PURPOSE: Studies show that axillary surgery can be potentially omitted in certain breast cancer patients who achieve breast pathologic complete response (pCR) after neoadjuvant systemic therapy (NST). However, potential differences between the ypT0 and ypTis subgroups remain to be explored. Furthermore, whether axillary surgery can be omitted in patients with clinically assessed positive axillary lymph nodes (cN+) remains unknown. This study was to evaluate the status of axillary lymph nodes for patients who achieved breast pCR after NST in the real-world study. METHODS: This retrospective cohort study included 258 patients with early or locally advanced breast cancer who underwent breast and axillary surgery after NST. Clinical and pathologic data were compared between patients with breast pCR (ypT0/is) and those without breast pCR. RESULTS: The rate of breast pCR after NST was 27.1% (70/258). Among the patients with initial cN0, the rate of axillary pCR was similar between the breast pCR and breast non-pCR groups (100% vs. 85.7%, P = 0.1543). Among those with breast pCR, the rate of axillary pCR was 100% in both the ypT0 and ypTis subgroups. Furthermore, among those with initial cN+, the rate of axillary pCR was higher in the breast pCR group than in the breast non-pCR group (82.7% vs. 22.9%, P < 0.0001). Among the patients with breast pCR, the rate of axillary pCR was higher in the ypT0 subgroup than in the ypTis subgroup (94.3% vs. 58.8%, P = 0.0034). CONCLUSION: Axillary surgery may potentially be omitted in patients with initial cN0 who achieve breast pCR (ypT0/is), and may also be considered for omission in patients with initial cN+ who achieve ypT0 (not ypTis).

Retrospective comparisons of nanoparticle albumin-bound paclitaxel and docetaxel neoadjuvant regimens for breast cancer.

Aim: To compare the efficacy and safety of 2-weekly nanoparticle albumin-bound paclitaxel (nP) and 3-weekly docetaxel regimens as neoadjuvant systemic therapy (NST) for breast cancer. Materials & methods: Patients (n = 201) received NST comprising either dose-dense epirubicin and cyclophosphamide followed by 2-weekly nP (n = 104) or 3-weekly courses of epirubicin and cyclophosphamide followed by docetaxel (n = 97). Results: Higher pathological complete response rates were achieved by the nP group. Subgroup analysis showed that the nP-based regimen achieved higher pathological complete response rates in patients with triple-negative tumor cells and high Ki67 levels. However, grades 3-4 peripheral sensory neuropathies were more frequent in the nP group. Conclusion: The 2-weekly nP-based regimen might be a better choice of NST for patients with breast cancer.