[Retracted] miR­143­5p suppresses breast cancer progression by targeting the HIF­1α­related GLUT1 pathway.

[This retracts the article DOI: 10.3892/ol.2022.13268.].

Patient-reported outcome (PRO)-based symptom assessment in patients with advanced lung cancer receiving first-line combination immunotherapy: a protocol for a multicenter, prospective, observational study.

BACKGROUND: Immunotherapy is currently applied in the first-line treatment regimens for numerous advanced cancers, especially advanced lung cancer. Immune-related adverse events (irAEs) resulting from immunotherapy can vary in severity and cause a substantial symptom burden to patients. However, there are limited data on symptom burden in patients with advanced lung cancer following immunotherapy. To address this deficit, this study aims to provide insight into the symptom burden and severity through patient-reported outcome measurements and conduct an analysis of temporal trends and clinical consequences of symptom burden in patients with advanced lung cancer receiving combination immunotherapy. METHODS: We will prospectively recruit 168 eligible patients from 14 hospitals in China. Eligible patients will be aged ≥ 18 years, pathologically diagnosed with locally advanced or stage IV primary lung cancer without surgical indications, and agreed to receive immunotherapy in combination with other therapies. The primary outcome of this study is the symptom burden of patients during the immunotherapy course. Longitudinal symptom data will be collected using the MD Anderson Symptom Inventory-Lung Cancer module (MDASI-LC) and the symptomatic irAEs scale at baseline (once before treatment) and weekly after treatment, until 1 month after the last treatment cycle has been completed. The trajectory of symptom burden following combination immunotherapy will be depicted, and by linking it to clinical outcomes (the secondary outcome and exploratory outcome of this study), the consequence of symptom burden in patients with advanced lung cancer receiving combination immunotherapy will be examined further. DISCUSSION: This study intends to establish longitudinal symptom trajectories in patients with lung cancer receiving immunotherapy, and explore its association with clinical outcomes. These findings may serve as an important reference for clinicians in the symptomatic management of patients with lung cancer receiving immunotherapy. TRIAL REGISTRATION NUMBER: ChiCTR2200061540. Registered on June 28, 2022.

Advances in the study of marketed antibody-drug Conjugates (ADCs) for the treatment of breast cancer.

Breast cancer continues to have a high incidence rate among female malignancies. Despite significant advancements in treatment modalities, the heterogeneous nature of breast cancer and its resistance to various therapeutic approaches pose considerable challenges. Antibody-drug conjugates (ADCs) effectively merge the specificity of antibodies with the cytotoxicity of chemotherapeutic agents, offering a novel strategy for precision treatment of breast cancer. Notably, trastuzumab emtansine (T-DM1) has provided a new therapeutic option for HER2-positive breast cancer patients globally, especially those resistant to conventional treatments. The development of trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) has further broadened the applicability of ADCs in breast cancer therapy, presenting new hopes for patients with low HER2 expression and triple-negative breast cancer. However, the application of ADCs presents certain challenges. For instance, their treatment may lead to adverse reactions such as interstitial lung disease, thrombocytopenia, and diarrhea. Moreover, prolonged treatment could result in ADCs resistance, complicating the therapeutic process. Economically, the high costs of ADCs might hinder their accessibility in low-income regions. This article reviews the structure, mechanism of action, and clinical trials of commercially available ADCs for breast cancer treatment, with a focus on the clinical trials of the three drugs, aiming to provide insights for clinical applications and future research.

miR-143-5p suppresses breast cancer progression by targeting the HIF-1α-related GLUT1 pathway.

Breast cancer (BC) is a commonly identified life-threatening type of cancer and a major cause of death among women worldwide. Several microRNAs (miRs), including miR-143-5p, have been reported to be vital for regulating hallmarks of cancer; however, the effect of miR-143-5p on BC requires further exploration. The present study performed bioinformatics analysis on GSE42072 and GSE41922 datasets from the National Center for Biotechnology Information Gene Expression Omnibus (GEO) database to identify miR-143-5p expression patterns. Furthermore, miR-143-5p expression was detected in BC cell lines and tissues via reverse transcription-quantitative PCR. Post-transfection with miR-143-5p mimics, Cell Counting Kit-8, colony formation and Transwell assays were performed to explore the effects of miR-143-5p on BC cell proliferation, colony formation, and migration. The association of miR-143-5p with the hypoxia-inducible factor-1α (HIF-1α)-associated glucose transporter 1 (GLUT1) pathway was explored via western blotting, immunofluorescence and dual-luciferase reporter assay. The present study detected high expression of miR-143-5p in BC tissue of the GSE42072 and serum of the GSE41922 datasets by GEO chip analysis. Additionally, the expression levels of miR-143-5p were decreased in BC tissues compared with those in adjacent healthy tissues, and low miR-143-5p expression was associated with a poorer prognosis and shorter survival time in patients with BC. In vitro, miR-143-5p expression levels were decreased in BC cells, and transfection with miR-143-5p mimics suppressed BC cell proliferation, colony formation, migration. Furthermore, miR-143-5p targeted the HIF-1α-related GLUT1 pathway, and inhibited HIF-1α and GLUT1 expression. Additionally, HIF-1α agonists reversed the miR-143-5p-induced inhibition during tumorigenesis. In conclusion, miR-143-5p exhibited low expression in BC tissues, and suppressed BC cell proliferation, colony formation, migration. Moreover, the antitumor effects of miR-143-5p targeted the HIF-1α-related GLUT1 pathway.

Clinical observation of the regeneration process of defects after breast cancer resection.

BACKGROUND: The present study aims to use two different kinds of filling materials, oxidized regenerated cellulose and gelatin sponge, to repair defects of breast-conserving surgery due to breast cancer, and compare the clinical efficacy, cosmetic effect and complication rate among groups. METHODS: A total of 125 patients, who had breast -conserving surgery due to breast cancer, were enrolled into the present study. Postoperative efficacy was assessed by a doctor and patient, according to the Harvard/NSABP/RTOG Breast Cosmetic Grading Scale. RESULTS: Among these patients, 41 patients received conventional breast-conserving surgery, and 84 patients received breast-conserving surgery plus filling implantation (41 patients in the oxidized regenerated cellulose group and 43 patients in the gelatin sponge group). All patients had small to medium sized breasts (cup size A and B). The average weight of tumor tissues was 56.61 ± 11.57 g in the conventional breast-conserving surgery group, 58.41 ± 8.53 g in the oxidized regenerated cellulose group, and 58.77 ± 9.90 g in the gelatin sponge group. The difference in pathological factors, average operation time, length of stay and local infection rate was not statistically significant among the three groups. 18 patients in the oxidized regenerated cellulose group and 15 patients in the gelatin sponge group were evaluated to have a good cosmetic effect by the surgeon and patient, while 12 patients in the conventional breast-conserving surgery group were evaluated to be have good cosmetic effect by the surgeon and patient. The cosmetic effects in the oxidized regenerated cellulose group and gelatin sponge group were comparable, and these were superior to those in the conventional breast-conserving surgery group. CONCLUSION: The use of oxidized regenerated cellulose and gelatin sponge is a feasible approach for defect repair after breast-conserving surgery.

Tumor-infiltrating lymphocytes benefit prediction of axillary pathologic response and prognostication of event-free survival in HER2-positive and biopsy-proven node-positive breast cancer treated with neoadjuvant therapy.

PURPOSE: The present study evaluated tumor-infiltrating lymphocytes (TILs) based on standardized scoring method and investigated its predictive value for axillary pathologic complete response (apCR) and prognostic significance for event-free survival (EFS) in neoadjuvant-treated HER2-positive breast cancer with initially biopsy-proven nodal metastasis. METHODS: We assessed TILs in a total of 187 pretherapeutic core biopsies of primary tumors. Receiver operating characteristic curve analysis was conducted to calculate the optimal cut-off point of TILs in discriminating axillary pathologic response. The associations of TILs with apCR or EFS were investigated by univariate and multivariate analyses. RESULTS: Receiver operating characteristic curve analysis identified a 10% cut-off point of TILs that optimally discriminated apCR from non-apCR (P < 0.001). High TILs were determined as TILs ≥ 10%, and tumor with TILs < 10% was defined as lymphocyte-depleted breast cancer (LDBC). The apCR rate of the entire cohort was 66.3% (124/187). Tumors with high TILs had a significantly higher apCR rate compared with LDBC (78.5% vs. 43.9%; P < 0.001). High TILs (P < 0.001), breast pathologic complete response (P = 0.006), and negative status of hormone receptor (P = 0.021) were independent predictors for apCR. High TILs were a markedly powerful predictor with an odds ratio of 4.01 (P < 0.001). EFS was significantly better among patients with high TILs than among those with LDBC (P < 0.001). Univariate and multivariate analyses indicated that high TILs (P = 0.019) and apCR (P = 0.013) were independent predictors for favorable EFS. CONCLUSIONS: TILs have predictive value for apCR and prognostic significance for EFS in initially node-positive and HER2-positive breast cancer treated with neoadjuvant therapy. LDBC (TILs < 10%) has a significantly unfavorable impact on apCR rate and EFS.

FOXC1-induced LINC01123 acts as a mediator in triple negative breast cancer.

BACKGROUND: MicroRNAs (miRNAs) representing a subclass of non-coding RNAs are dynamically expressed and participate in multiple pathological responses, whereas, the expression pattern or function of miRNAs has not been fully addressed in triple-negative breast cancer (TNBC). Currently we concentrate on dissecting the probable role of microRNA-663a (miR-663a) in TNBC cellular processes. METHODS: qRT-PCR detected the expression of miR-663a in TNBC cells. Besides, we monitored the effects of miR-663a on TNBC proliferation and apoptosis. On the basis of bioinformatics assistance and mechanical validation, we identified the miRNA-sponging role of LINC01123 and downstream target of miR-663a in TNBC was assessed and verified. The transcription activation of was explored via ChIP and luciferase reporter assays. RESULTS: In comparison to MCF-10A, we certified the downregulation of miR-663a in TNBC cell lines. Augmentation of miR-663a was anti-proliferation and pro-apoptosis in TNBC cell lines. LINC01123 protected CMIP against miR-663a suppression through acting as a sponge of miR-663a in TNBC. LINC01123 was transcriptionally induced by FOXC1. Rescue experiment proved that miR-663a suppression or CMIP (c-Maf inducing protein) enhancement could countervail LINC01123 depletion-mediated effects on TNBC cellular processes. CONCLUSION: LINC01123, activated by FOXC1, regulated TNBC growth through miR-663a/CMIP signaling, which unveiled a new functional pathway of FOXC1-induced LINC01123/miR-663a/CMIP in TNBC.

MicroRNA-10b expression in breast cancer and its clinical association.

MicroRNAs (miRNAs) are short non-coding RNA molecules that play a significant role in many types of cancers including breast cancer. In the current study, we evaluated the expression levels of microR-10b (miR-10b) in 115 breast cancer patients from Sichuan Cancer Center. Real time reverse transcription-PCR was used to assess miR-10b expression. Clinical data including disease stage, survival status, age, ER/PR/HER2 status, molecular subtypes, tumor size, lymph node status and Ki-67 expression levels were correlated with miR-10b expression levels. Our data showed that the miR-10b expression is correlated with disease stage, living status and tumor sizes. We also found that miR-10b expression levels are higher in the lymph node positive group and the Ki-67 higher scoring group (score > 20). No statistically significant differences were observed based on age or molecular sub-type grouping. In conclusion, miR-10b may be a biomarker for breast cancer and is a potential treatment target.

MicroRNA-588 is downregulated and may have prognostic and functional roles in human breast cancer.

BACKGROUND We explored the expression pattern, prognostic potential, and functional role of microRNA-588 (miR-588) in human breast cancer (BC). MATERIAL AND METHODS The expression pattern of miR-588 was assessed by qPCR in BC cell lines and human BC carcinomas. The correlations between miR-588 and BC patients' clinicopathological characteristics, as well as BC patients' overall survival, were statistically assessed. In in vitro culture, MCF-7 and MDA-MB-231 cells were infected with lentivirus to overexpress endogenous miR-588. The subsequent effects of miR-588 upregulation on BC cell proliferation and cisplatin chemosensitivity were examined. RESULTS miR-588 was found to be significantly downregulated in both BC cell lines and carcinoma tissues of BC patients. Low expression of miR-588 was closely correlated with BC patients' poor prognosis of TNM stage, lymph node metastasis, and estrogen receptor status. In addition, patients with low miR-588-expressing carcinomas had much shorter overall survival. In MCF-7 and MDA-MB-231 cells, lentiviral infection induced significant miR-588 upregulation, and miR-588 upregulation had an anti-tumor effect in BC cells by significantly inhibiting cancer proliferation and increasing cisplatin chemosensitivity. CONCLUSIONS miR-588 is downregulated in BC and its aberrant expression is closely associated with patients' poor prognosis and overall survival, thus suggesting a biomarker role. miR-588 also has anti-tumor function in BC, making it a potential therapeutic target for BC treatment.

[The expression and clinical significance of Wnt-1 induced secreted protein-1 in breast carcinoma].

OBJECTIVE: To investigate the expression of Wnt-1 induced secreted protein-1 (WISP-1) between breast cancer and paired normal breast tissues and to explore the significance of WISP-1 in breast cancer tumorigenesis. METHODS: The mRNA and protein expressions of WISP-1 in human breast cancer were measured by Quantitative Real-Time RT-PCR and immunohistochemical staining and further analyzed the relationship between WISP-1 expression and clinic pathologic characters. RESULTS: WISP-1 expression in breast cancer was higher than that in normal breast tissue (P = 0.001). The mRNA expression level of WISP-1 was correlated with tumor size, staging, lymph node status, differentiated degree and HER-2 status (P < 0.05). WISP-1 protein expression level was correlated with lymph node status, differentiated degree and HER-2 status (P < 0.05). CONCLUSION: WISP-1 expression in human breast cancer increases significantly and may play a key role in the invasion and metastasis of human breast cancer.

[A study on the effect of Tanshinone II A against human breast cancer in vivo].

OBJECTIVE: To confirm Tanshinone II A's (Tan II A) anti-cancer activity on nude mice bearing human breast cancer cells with estrogen receptor (ER) positive and negative and to elucidate the mechanism of its activity in vivo. METHODS: Established the animal model of nude mices bearing human breast cell, both ER positive MCF-7 and ER negative MDA-MB-231, each group was divided into 3 subgroups, respectively by intraperitoneal injection of Tan II A at a dose of 30 mg/kg 4 times/week, by gavage of Tamoxifen at a dose of 1 mg/kg 7 times/ week and by solvent control for 4 weeks. All animals were tested for anti-cancer activity including the weights and the volumes of the tumor, apoptosis index by flow cytometry and expression of p53, bcl-2, cerbB-2 by immunohistochemistry method after the treatment. RESULTS: In MCF-7 group, there were a 33.64% tumor mass volume reduction and a 32.24% tumor mass weight reduction after Tan II A treatment; in MDA-MB-231 group, a 38.34% tumor mass volume reduction and a 39.82% tumor mass weight reduction were observed in Tan II A subgroups; the differences between Tan II A and Tamoxifen or solvent control were statistically significant in both groups (P < 0.05); increase of apoptosic fiction by flow cytometry examination in Tan II A subgroups in both MCF-7 (48.31% +/- 5.84%) and MDA-MB-231(50.25% +/- 5.03%) groups were observed, there were both significant differences between Tan II A and the other subgroups (P < 0.05). Statistically significant decrease of p53 and bcl-2 expression were observed in Tan lI A between solvent control subgroup in both MCF-7 and MDA-MB-231 groups (P < 0.05) while cerbB-2 had no significant difference with control group (P > 0.05). CONCLUSION: Tan lI A can inhibit both breast cancer cell MCF-7 and MDA-MB-231 growth in vivo, which had better anti-cancer effect than Tamoxifen. The mechanism may be associated with the induction of apoptosis, down regulation of the expression level of gene bcl-2 and p53, but may not with the expression level of cerbB-2.

Experimental study of the anti-cancer mechanism of tanshinone IIA against human breast cancer.

Tanshinone IIA is a widely used Chinese herbal medicine isolated from Danshen (Salvia miltiorrhiza). Recent studies indicate that tanshinone IIA may have anti-inflammatory and anti-oxidant properties, as well as cytotoxic activities against multiple human cancer cell lines. This study was performed to determine the anti-cancer activity of tanshinone IIA on human breast cancer cells in vitro and in vivo and to elucidate the underlying mechanism of this activity. Human breast cancer cell lines (estrogen receptor-positive and -negative) were treated with tanshinone IIA and tamoxifen. The inhibitory effects of tanshinone IIA and tamoxifen on breast cancer cell proliferation were examined using MTT assays, BrdU incorporation, immunohistochemistry and flow cytometry. Upon treatment with tanshinone IIA, breast cancer cell proliferation was significantly inhibited in a dose- and time-dependent manner (IC50 = 0.25 microg/ml) and apoptotic cell populations increased, while tamoxifen inhibited only ER-positive breast cancer cells prominently and had no effect on ER-negative cells. In addition, tamoxifen had significantly weaker inhibitory effect than tanshinone IIA on ER-positive breast cancer cells in vitro and in vivo. Furthermore, tanshinone IIA decreased the expression of P53 and bcl-2, but not of cerbB-2, in estrogen receptor-positive and negative xenografted nude mice. Our findings suggest that tanshinone IIA might have potential anti-cancer activity that is stronger than tamoxifen in both ER-positive and ER-negative breast cancers. This function could be attributed in part to its inhibition of proliferation and apoptosis induction in cancer cells via the downregulation of multiple genes involved in cell cycle regulation, cell proliferation, apoptosis and DNA synthesis.

[A study on anticancer activity of tanshinone II A against human breast cancer].

OBJECTIVE: To investigate the proliferation inhibition and apoptosis-associated genes expression of both human breast cancer cells with estrogen receptor (ER) positive and negative (MCF-7 and MDA-MB-231) which treated with tanshinone II A, and to elucidate its mechanism of activity. METHODS: Human ER positive breast cancer cells (MCF-7) and ER negative cells (MDA-MB-231) were tested in vitro for cytotoxicity of tanshinone II A with MTT method. The effect of tanshinone II A on DNA synthesis and apoptosis of both human breast cancer cells were evaluated with Brdu incorporation and flow cytometry. Immunohistochemistry were applied to test the P53, CerBb-2 and Bcl-2 protein expression of both cells. RESULTS: After Tanshinone II A treatment, a dose- and time-dependent decreased proliferation in both MCF-7 and MDA-MB-231 cells were observed (P < 0.05) with a IC50 0.25 microg/mL. A decreased BrdU incorporation and an increased apoptosis in both cells were also observed (P < 0.05 and P < 0.01 respectively). Immunohistochemistry test demonstrated that tanshinone A upregulate P53 expression in both cells and also weakly upregulate the CerBb-2 expression in MCF-7 (P < 0.05), whereas no influence on CerBb-2 expression of MDA-MB-231 and on Bcl-2 expression of both cells were demonstrated (P > 0.05). CONCLUSION: This study suggested that tanshione II A could inhibit the proliferation, induce apoptosis of ER-positive breast cancer cell MCF-7 and ER-negative breast cancer cell in vitro. The mechanism may be associated with the inhibition of DNA synthesis, induction of apoptosis, but may not with the expression level of gene p53, cer Bb-2 and bcl-2.