Path to pollution and carbon reduction synergy from the perspective of the digital economy: Fresh evidence from 292 prefecture-level cities in China.

The digital economy is a crucial focus for realizing the transformation of old and new kinetic energy in China. It is widely integrated with various fields of the economy and society, constantly providing a new dynamic mechanism with synergetic control of environmental pollution and carbon emissions (SCEPCE). Based on panel data from 292 prefecture-level cities in China from 2011 to 2021, this study discusses the spatial effects and mechanisms of the digital economy on the coordinated control of pollutants and carbon emissions. The study found that: (1) The digital economy has direct and indirect influences on the coordinated control of pollutants and carbon emissions. The digital economy can drive reductions in pollutants and carbon dioxide emissions by upgrading industrial structures and transforming energy structures. (2) Green innovation plays an active regulatory role in the digital economy and structural optimization, particularly in the context of SCEPCE. This interference helps mitigate the impact of the digital economy on pollution and carbon emissions. (3) The digital economy has a significant spatial spillover effect on the coordinated control of pollutants and carbon emissions. (4) The influence mechanism of the digital economy on pollution reduction and carbon reduction synergy exhibits geographical heterogeneity, resource endowment heterogeneity. To enhance the synergy of pollution reduction and carbon reduction, it is essential to bolster support and optimise the digital economy at various levels. This includes reinforcing regional balance, considering spatial spillover effects, and enhancing the leading role of developed cities in the region.

LncRNA TDRKH-AS1 promotes breast cancer progression via the miR-134-5p/CREB1 axis.

BACKGROUND: Breast cancer (BC) is a prevalent malignancy with complex etiology and varied clinical behavior. Long non-coding RNAs (lncRNAs) have emerged as key regulators in cancer progression, including BC. Among these, lncRNA TDRKH-AS1 has been implicated in several cancers, but its role in BC remains unclear. METHODS: We conducted a comprehensive investigation to elucidate the role of TDRKH-AS1 in BC. Clinical samples were collected from BC patients, and BC cell lines were cultured. Bioinformatics analysis using the starBase database was carried out to assess TDRKH-AS1 expression levels in BC tissue samples. Functional experiments, including knockdown, colony formation, CCK-8, Transwell, and wound-healing assays, were conducted to determine the role of TDRKH-AS1 in BC cell proliferation and invasion. Luciferase reporter and RIP assays were used to examine the interactions between TDRKH-AS1 and miR-134-5p. In addition, the downstream target gene of miR-134-5p, cAMP response element-binding protein 1 (CREB1), was identified and studied using various methods, including RT-qPCR, immunoprecipitation, and rescue experiments. In vivo experiments using mouse tumor xenograft models were conducted to examine the role of TDRKH-AS1 in BC tumorigenesis. RESULTS: TDRKH-AS1 was found to be significantly upregulated in BC tissues and cell lines. High TDRKH-AS1 expression correlated with advanced BC stages and worse patient outcomes. Knockdown of TDRKH-AS1 led to decreased BC cell proliferation and invasion. Mechanistically, TDRKH-AS1 acted as a sponge for miR-134-5p, thereby reducing the inhibitory effects of miR-134-5p on CREB1 expression. Overexpression of CREB1 partially rescued the effects of TDRKH-AS1 knockdown in BC cells. In vivo studies further confirmed the tumor-promoting role of TDRKH-AS1 in BC. CONCLUSIONS: Our study unveiled a novel regulatory axis involving TDRKH-AS1, miR-134-5p, and CREB1 in BC progression. TDRKH-AS1 functioned as an oncogenic lncRNA by promoting BC cell proliferation and invasion through modulation of the miR-134-5p/CREB1 axis. These findings highlighted TDRKH-AS1 as a potential diagnostic biomarker and therapeutic target for BC treatment.

Off-On Squalene Epoxidase-Specific Fluorescent Probe for Fast Imaging in Living Cells.

SQLE (squalene epoxidase) is a cell membrane-bound enzyme. It is a target of fungicides and may become a new target for cancer therapy. Therefore, monitoring the content and distribution of the key enzyme in living cells is very challenging. To achieve this goal, tetraphenyl ethylene-Ter (TPE-Ter) was first designed as a new fluorescent probe to SQLE based on its active cavity. Spectral experiments discovered that SQLE/TPE-Ter shows stronger emission with fast response time and low interference from other analytes. Molecular dynamics simulation clearly confirmed the complex structure of SQLE/TPE-Ter, and the key residues contribute to restriction of TPE-Ter single-molecular motion in the cavity. TPE-Ter-specific response to SQLE is successfully demonstrated in living cells such as LO2, HepG2, and fungi. Imaging of TPE-Ter-treated fungi indicates that it can be used to rapidly assess antifungal drug susceptibility (30 min at least). The present work provides a powerful tool to detect content and distribution of SQLE in living cells.

The Dysregulated Expression of KCNQ1OT1 and Its Interaction with Downstream Factors miR-145/CCNE2 in Breast Cancer Cells.

BACKGROUND/AIMS: Next-generation sequencing (NGS) has revealed abundant long noncoding RNAs (lncRNAs) that have been characterized as critical components of cancer biology in humans. The present study aims to investigate the role of the lncRNA KCNQ1OT1 in breast cancer (BRCA) as well as the underlying molecular mechanisms and functions of KCNQ1OT1 involved in the progression of BRCA. METHODS: The Cancer Genome Atlas (TCGA) and StarBase v2.0 were used to obtain the required gene data. Dual luciferase reporter gene assays were conducted to verify the relevant intermolecular target relationships. QRT-PCR and Western blot were performed to measure the expression levels of different molecules. Cell proliferation was detected by using the MTT and colony formation assays, while cell migration and invasion were examined by transwell assay. Variations in cell apoptosis and cell cycle were determined through flow cytometry. A tumor xenograft model was applied to assess tumor growth in vivo. RESULTS: KCNQ1OT1 was found to be remarkably highly expressed in BRCA tissues and cells. KCNQ1OT1 modulated CCNE2 through sponging miR-145 in BRCA. KCNQ1OT1 promoted tumor growth in vivo by regulating miR-145/CCNE2. CONCLUSION: The KCNQ1OT1/miR-145/CCNE2 axis plays a critical regulatory role in BRCA, potentially giving rise to BRCA tumorigenesis and progression. These findings provide valuable evidence for improving the diagnosis and treatment of BRCA in the future.

Heading towards carbon neutrality: how do marine carbon sinks serve as important handle for promoting marine ecological civilization construction?

As an efficient long-term carbon sink, marine carbon sinks and the associated carbon sink effects, technology, accounting and trading market construction warrant investigation across various disciplines. However, information on the interrelationships and their development over time with respect to the research conducted in China is limited, affecting the ability to drive research directions and optimize continued advancement in this field. Therefore, in this study, we aimed to understand the current situation of marine carbon sink research in China to promote a deeper level of scientific development based on the research literature related to marine blue carbon sinks in the core databases of the China National Knowledge Internet (CNKI) and Web of Science (WOS). We used bibliometric tools in the Citespace software to quantitatively compare and analyse the main characteristics of marine blue carbon sink research including publication volume, time, journals, authors and institutions. We also explored the popular research topics, frontier areas, and theme evolution trends through keyword clustering and emergent and co-occurring knowledge maps. The key recommended research directions for ocean carbon sinks are: (1) to promote the unified carbon sink market research of land and sea integration through multidisciplinary and cross-disciplinary research; (2) to achieve new breakthroughs in ocean carbon sinks with the support of coastal wetlands and seawater offshore aquaculture environments; (3) to explore the protection provided by ocean carbon sinks with a comprehensive eco-compensation mechanism; (4) to improve the application of marine carbon sinks by taking the theory and technological innovation research related to marine carbon sinks as the guide. Ultimately, our work helps characterise the current situation of marine carbon sink research, promote the research in this field to a deeper level of development and provide reference for subsequent scholars to carry out related research.

The Value of Neoadjuvant Anthracycline-Based Regimens for HER2-Positive Breast Cancer: A Systematic Review and Meta-analysis Including 1366 Patients.

Background: The standard recommendation for neoadjuvant therapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer patients is trastuzumab in combination with chemotherapy, but there is no current standard recommendation for appropriate chemotherapy regimens. This meta-analysis evaluated the efficacy and cardiac safety of the concurrent use of anti-HER2 targeted drugs and anthracycline-based neoadjuvant chemotherapy (NAC) for HER2-positive breast cancers. Methods: The pooled odds ratio (OR) rate for pathologic complete response (pCR), the pooled hazard ratio (HR) of overall survival (OS), and the left ventricular ejection fraction (LVEF) decline events were all calculated. Differences in efficacy, prognosis, and cardiac safety were compared between patients receiving an anthracycline-containing regimen (AB) and those treated with non-anthracycline-based (nAB) NAC. Results: A total of 1366 patients in 4 prospective and 3 retrospective studies were included in the meta-analysis. The pooled OR for pCR rate was 0.73 with a 95% confidence interval (CI) of 0.43 to 1.24 (P = .246). Subgroup analysis of low tumor burden cases showed no improvement in pCR rate for patients in the AB group compared with nAB, with the pooled OR rate being 0.73 with a 95% CI of 0.37 to 1.44 (P= .357). The 3-year OS rate was 95.63% and 95.54% in the AB and nAB groups, respectively, with no statistical difference (P= .157). There was a significant increase in the rate of LVEF decline of 19.07% in the AB group compared with 13.33% for the nAB group, with an HR of 1.62 and a 95% CI of 1.11 to 2.36 (P = .013). Conclusions: The addition of anthracyclines did not improve pCR rates and survival after neoadjuvant and the increased cardiotoxicity of anthracyclines further limited their application. This study showed that it was feasible to use anti-HER2 drugs without anthracyclines in neoadjuvant therapy for HER2-positive breast cancer patients.

Neoadjuvant Pyrotinib plus Trastuzumab, Docetaxel, and Carboplatin in Early or Locally Advanced Human Epidermal Receptor 2-Positive Breast Cancer in China: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial.

INTRODUCTION: This multicenter, randomized, double-blind, placebo-controlled phase 2 trial compared the efficacy, and safety of adding pyrotinib to trastuzumab, docetaxel, and carboplatin versus placebo, trastuzumab, docetaxel, and carboplatin in Chinese patients with human epidermal receptor 2 (HER2)-positive early or locally advanced breast cancer (ClinicalTrials.gov identifier: NCT03756064). METHODS: Sixty-nine women with HER2-positive early (T1-3, N0-1, M0) or locally advanced breast cancer (T2-3, N2 or N3, M0; T4, any N, M0) were recruited from October 1, 2019, to June 1, 2021. Before surgery, patients received 6 cycles of orally pyrotinib (400 mg once per day), trastuzumab (8-mg/kg loading dose and 6-mg/kg maintenance doses), docetaxel (75 mg/m2), and carboplatin (AUC = 6 mg/mL·min) or orally placebo, trastuzumab, and docetaxel, and carboplatin every 3 weeks. The primary end point was independent review committee-assessed total pathologic complete response rate. The 2-sided Cochran-Mantel-Haenszel test, stratified by age, hormone receptor status, tumor stage, nodal status, cTNM stage, and Ki-67 level was used to compare rates between treatment groups. RESULTS: In total, 69 female patients were randomized (pyrotinib, 36; and placebo, 33; median age, 53 [31-69] years). In the intention-to-treat population, total pathologic complete response rates were 65.5% (19/29) in the pyrotinib group and 33.3% (10/30) in the placebo group (difference, 32.2%, p = 0.013). Diarrhea was been reported in 86.1% of patients (31/36) in the pyrotinib group as the most common adverse events (AEs) and 15.2% of patients (5/33) in the placebo group. But no grade 4 or 5 AEs were reported. CONCLUSION: Treatment with pyrotinib, trastuzumab, docetaxel, and carboplatin resulted in a statistically significant improvement in the total pathologic complete response rate versus placebo, trastuzumab, docetaxel, and carboplatin for the neoadjuvant treatment of HER2-positive early or locally advanced breast cancer in Chinese patients. Safety data were in line with the known pyrotinib safety profile and generally comparable between treatment groups.

A xanthene-based fluorescent probe for detection of peroxynitrite in living cells and zebrafish.

Peroxynitrite (ONOO-) is one of quite critical reactive oxygen species that acts critical roles in a number of diverse biological functions and pathological events. Notably, excessive ONOO- will lead to sorts of diseases. Thus, monitoring of endogenous ONOO- levels will be conducive to exploring the physiological activities and functions of ONOO-. Here, a simple turn-on fluorescent probe named DMX is reported using CN bond as the ONOO- recognition site and xanthene as the fluorophore. DMX possessed a good linear dependence with ONOO- concentration (0-9 µM), highly sensitive detection (DL = 37 nM), and excellent selectivity towards ONOO-. What is more, the biological experiments reveal that DMX is able to be utilized to track exogenous/endogenous ONOO- employing confocal laser scanning microscopy. Visualization of ONOO- in zebrafish was also successfully conducted, suggesting that DMX might be used to study ONOO- roles in vivo. We believe that DMX will have potential for exploring the pivotal role of ONOO- during all sorts of physiological and pathological activities.

A deep red ratiometric fluorescent probe for accurate detection of peroxynitrite in mitochondria.

Peroxynitrite (ONOO-) is widespread within living organisms and has been implicated in many physiological and pathological processes. Since ONOO- is mainly produced in mitochondria, accurate detection of ONOO- in mitochondria can help us understand its specific mechanism of action in the organism. Rather than single-wavelength emissive mitochondrial probes, ratiometric fluorescent probes with longer emission wavelength, large emission shift, and specific mitochondrial targeting properties are more likely to obtain a more accurate ONOO- content in mitochondria. To further avoid the interference by cytoplasmic ONOO-, we constructed a fluorescent probe MXMP with deep red emission and ratio properties, and it will be forbidden to enter the mitochondria after oxidation. In addition to its excellent selectivity and sensitivity, it shifted its fluorescence emission by up to 130 nm, with a detection limit of 84 nM.

Effects of Gonadotropin-Releasing Hormone Analogs on Ovarian Function Against Chemotherapy-Induced Gonadotoxic Effects in Premenopausal Women With Breast Cancer in China: A Randomized Clinical Trial.

IMPORTANCE: Studies of the use of gonadotropin-releasing hormone analogs (GnRHa) to protect ovarian function have shown mixed results. OBJECTIVE: To determine whether administering GnRHa during chemotherapy in premenopausal women with breast cancer can reduce ovarian impairment. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial, conducted at the Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital and Zhejiang Cancer Hospital in China, was an open-label trial involving premenopausal women aged 18 to 49 years with operable stage I to III breast cancer for which treatment with adjuvant or neoadjuvant cyclophosphamide-containing chemotherapy was planned in 2 parallel groups: treatment with chemotherapy with or without GnRHa. Enrollment occurred from September 2015 to August 2017, and follow-up ended December 2020. The data were analyzed in March 2021. A total of 405 patients were enrolled in the study, among whom 27 patients (6.7%) quit participation voluntarily, 33 (8.1%) did not meet the inclusion criteria and were excluded, and 15 (3.7%) were lost to follow-up. Ultimately 330 patients were included in the primary analysis, including 29 patients with baseline anti-Müllerian hormone levels less than 0.5ng/ mL. INTERVENTIONS: Eligible patients were randomly assigned (1:1) to receive chemotherapy with (n = 165) or without (n = 165) GnRHa. In patients randomized to receive GnRHa, 3.6 mg of goserelin or 3.75 mg of leuprorelin was injected subcutaneously once every 28 days from 1 to 2 weeks before the first cycle of chemotherapy to 4 weeks after the last cycle of chemotherapy. MAIN OUTCOMES AND MEASURES: The primary end point was the rate of premature ovarian insufficiency (POI) at 12 months after chemotherapy. Premature ovarian insufficiency was defined as anti-Müllerian hormone levels of less than 0.5 ng/mL in this study. The secondary end point was overall survival (OS) and tumor-free survival (TFS). RESULTS: A total of 330 eligible patients could be evaluated with complete data, among whom 301 patients (91.2%; GnRHA group: mean [SD] age, 40.6 [6.7] years; control group: mean [SD] age, 40.2 [5.9] years) were eligible for primary end point analysis. At 12 months after the completion of chemotherapy, the POI rate was 10.3% (15 of 146) in the GnRHa group and 44.5% (69 of 155) in the control group (odds ratio, 0.23; 95% CI, 0.14-0.39; P < .001). Anti-Müllerian hormone resumption in the GnRHa group was significantly better than that in the control group (15 of 25 vs 6 of 44; odds ratio, 4.40; 95% CI, 1.96-9.89; P < .001). After a median follow-up of 49 months (range, 25-60 months), the differences in 4-year OS and TFS between the 2 groups were not significant. A post hoc analysis showed that in patients younger than 35 years, the TFS was higher in the GnRHa group than in the control group (93% vs 62%; P = .004; hazard ratio, 0.15; 95% CI, 0.03-0.82; P = .03). CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that administering GnRHa in treatment with chemotherapy for premenopausal patients with breast cancer reduces the risk of POI, which promotes the recovery of ovarian function. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02518191.

A Nomogram to Predict Disease-Free Survival Following Neoadjuvant Chemotherapy for Triple Negative Breast Cancer.

BACKGROUND: Neoadjuvant chemotherapy (NACT) is considered a standard treatment strategy for locally advanced triple negative breast cancer (TNBC). TNBC patients who achieve a pathologic complete response (pCR) are predicted to have a better prognosis while unfavorable chemo-sensitivity is still associated with a higher risk of disease relapse. The objective of this study was to construct a nomogram to predict disease-free survival (DFS) for TNBC patients following NACT. METHODS: A total of 165 TNBC patients who underwent standard NACT and surgery were retrospectively reviewed, and data on their clinicopathological factors before and after NACT were collected. Independent prognostic factors for DFS were identified by Cox regression based on lower Akaike information criteria (AIC) and Bayesian information criterion (BIC). A nomogram to predict the 2-year and 5-year DFS following NACT for TNBC was constructed based on training cohort (n = 132) and validated by a validation cohort (n = 33). RESULTS: Either limited or full pCR (breast-only pCR, node-only pCR, or both-pCR) indicated significantly improved DFS and overall survival (OS) (p < 0.001). Lager residual tumor size (hazard ratio [HR] 1.175, p = 0.011) and the presence of lymphatic vessel invasion (LVI) (HR 3.168, p = 0.001) were identified as independent predictors of disease relapse in the training cohort. Five variables, including age, primary tumor size, histological grade, residual tumor size, and LVI were used to establish the nomogram. The C-index of the nomogram was 0.815, and calibration curves showed an acceptable consistency between the actual and nomogram-predicted 2-year and 5-year DFS. The proposed nomogram demonstrated superior predictive performance compared with Residual Cancer Burden (RCB) classification and the 8th American Joint Committee on Cancer Post Neoadjuvant Therapy Classification (AJCC ypTNM) staging system (area under the curve [AUC] for 2-year DFS: 0.870 vs. 0.758 vs. 0.711, respectively; AUC for 5-year DFS: 0.794 vs. 0.731 vs. 0.702, respectively) in the validation cohort. CONCLUSIONS: The nomogram proposed in our study enabled to quantify the risk of disease relapse and demonstrated superior predictive performance than a survival predict instrument. It was an easy-to-use tool for clinicians to guide individualized surveillance of TNBC patients following standard NACT.

The Guiding Significance of the Number of Positive Sentinel Lymph Nodes in Frozen Section for Intraoperative Axillary Dissection in Early Breast Cancer.

PURPOSE: The results of large randomised trials have changed the treatment strategy of axillary lymph nodes. Axillary lymph node dissection (ALND) can be avoided in some patients with one to two sentinel lymph nodes (SLNs) metastasis based on final paraffin section (FPS) results which called into question the need for intraoperative frozen section (FS). This study aims to assess the guiding value of the number of positive SLN detected via FS for intraoperative ALND. PATIENTS AND METHODS: This study retrospectively analyzed data from 3303 patients with breast cancer who underwent SLN biopsy between 2015 and 2019. Combined with the FPS results, FS sensitivity, specificity, and false negative rate (FNR) were calculated and the difference in the number of positive SLNs between FS and FPS was analyzed. RESULTS: The overall FNR of FS was 23.21%, which was 76.47% in isolated tumor cells, 62.28% in micrometastasis, and 12.09% in macrometastatic disease. The size of SLN metastasis were significantly associated with a higher FNR (p<0.001). The accuracy rate of the number of positive SLNs detected via FS was 92.62%. Human epidermal growth factor receptor 2 (HER2) (p<0.03) and Ki67 (p<0.02) were significant factors affecting the accuracy rate. CONCLUSION: FS is a effective method for SLN biopsy, ALND can be avoided in patients with one or two positive SLNs detected via FS.

SC-SC Anion-Assisted Linker Exchange within a Three-Dimensional Cu(II)-Triazole Framework: A Luminescent Probe for S2.

A three-dimensional (3D) binodal 3,5-connected net, {[Cu(MTP)(H2O)](NO3)}n (1) with the Schläfli symbol of {3·72}{32·75·83} can be transformed into a two-dimensional (2D) kagóme network with the Schlafli symbol of {32·62·72} in an irreversible single crystal-single crystal (SC-SC) guest-assisted linker exchange process. The product of this SC-SC represents the first luminescent probe for S2- based on triazole ligand.

Effect of cimicifuga racemosa on menopausal syndrome caused by LHRH-a in breast cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Cimicifuga racemose is previously proved effective on nature menopausal syndrome (MPS). However, its clinical value in treating with MPS induced by luteinizing-hormone releasing hormone analogue (LHRH-a) therapy of pre-/peri-menopausal breast cancer patients is still unknown. AIM OF STUDY: This perspective randomised-design study is to investigate the effect and safety of cimicifuga racemosa on MPS induced by LHRH-a in breast cancer (clinical trial registered: NCT03339882). MATERIALS AND METHODS: Breast cancer patients planning for LHRH-a treatment were randomly divided into 2 groups. The control group which was being treated with the standard treatment of LHRH-a. The other group was being treated with Remifemin, the commercialized product of cimicifuga racemose extract, combined with LHRH-a, called Remifemin group. Our main endpoint was Kupperman menopause index (KMI). Hormone levels in peripheral blood and gynecological complications were also evaluated. RESULTS: Totally, 85 patients (42 in Remifemin group and 43 in control group) were enrolled in Zhejiang Cancer Hospital. At the 4th, 8th and 12th week after using LHRH-a, the KMI were all significantly lower in Remifemin group than in control group (P < 0.01), while the hormone levels, including estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were similar in the two groups. In addition, the incidence of cervical cyst in Remifemin group was higher than that in control group (P = 0.02), and there was no significant difference in the other gynecological complications, including endometrial thickening, ovarian cyst or uterine fibroid (P > 0.05). CONCLUSIONS: Cimicifuga racemose is effective, oncological safe and reliable for treatment of MPS caused by LHRH-a in breast cancer.

Knockdown of ribosomal protein S15A inhibits proliferation of breast cancer cells through induction of apoptosis in vitro.

To explore the role of ribosomal protein S15A (RPS15A) in breast cancer. The Oncomine database was used to compare the expression of RPS15A in human breast cancer tissues and normal tissues. RPS15A in breast cancer cell line ZR-75-30 and BT474 was specifically knocked down using lentivirus-mediated short hairpin RNAs (shRNAs). RPS15A knockdown efficiency was validated by quantitative polymerase chain reaction and western blot analysis. Subsequently, the functional effects of RPS15A on proliferation of breast cancer cells were investigated by MTT, colony formation and flow cytometry assays. Functional analysis indicated that RPS15A knockdown could inhibit cell proliferation, induced cell cycle arrest and apoptosis. Mechanism analysis revealed RPS15A mediated apoptosis via activating of caspase-3 and PARP cleavage, upregulating of Bad and BAX and downregulating of Bcl-2. Our preliminary study highlighted the importance of RPS15A in breast cancer growth. The inhibition of RPS15A may be a promising therapeutic target for breast cancer treatment.

The effect of adjuvant chemotherapy in male breast cancer: 134 cases from a retrospective study.

BACKGROUND: Male breast cancer (BC) is a kind of rare tumour. There were few researches concerning the effect of chemotherapy for it. The purpose of this study is to estimate the value of chemotherapy on prognosis in male BC. PATIENTS AND METHODS: Complete clinical and pathological information of male BC were collected from January 1990 to January 2008 in Zhejiang Cancer Hospital in China. 134 cases of male BC were included for analysis and separated into two groups based on receiving chemotherapy or not receiving chemotherapy. The disease-free survival (DFS) and overall survival (OS) between chemotherapy group and non-chemotherapy group were compared with Kaplan-Meier survival curve. Stratified analysis was used to evaluate the strength of the association between chemotherapy and each risk factor. Multivariate analysis was conducted by using COX proportional hazard regression model. RESULTS: There were 58.21% (78/134) cases who underwent chemotherapy and 41.79% (56/134) cases without chemotherapy. There were 20 cases (25.64%) with recurrence/metastasis in patients with chemotherapy and six cases (10.71%) in patients without chemotherapy. The mean DFS time of male BC with chemotherapy and non-chemotherapy is 150.87 and 154.13 months, respectively (χ2=3.825, p=0.050). The mean OS time of male BC with chemotherapy and non-chemotherapy is 155.33 and 154.26 months, respectively (χ2=2.542, p=0.111). COX proportional hazard regression model showed that the two groups had similar DFS (HR=0.386, p=0.165), while chemotherapy might be a protective fact on OS (HR=0.140, p=0.026). CONCLUSION: The utility of chemotherapy should be considered in the high risk level of recurrence/metastasis in male BC.

ICT1 knockdown inhibits breast cancer cell growth via induction of cell cycle arrest and apoptosis.

The protein encoded by immature colon carcinoma transcript 1 (ICT1) is a component of the human mitochondrial ribosome, and is reported to be implicated in cell proliferation, viability and apoptosis of HeLa cells. This study was conducted to investigate the role of ICT1 in human breast cancer. Oncomine database was used to investigate ICT1 expression in human breast cancer tissues compared to normal tissues. The results showed that ICT1 was highly overexpressed in various human breast cancer subtypes. Then short hairpin RNA (shRNA)-mediated knockdown of ICT1 was performed in human breast cancer ZR-75-30 and T-47D cells. A series of functional analysis, including MTT, colony formation and flow cytometry assays were conducted after ICT1 knockdown. Our results demonstrated that knockdown of ICT1 significantly suppressed cell viability and proliferation through cell cycle arrest at the G2/M phase and induced apoptosis in breast cancer cells. Furthermore, knockdown of ICT1 altered signaling pathways associated with cell growth and apoptosis, including phospho­BAD (Ser112), phospho-PRAS40 (Thr246) and induction of phospho­AMPKα (Thr172). Additionally, it was further confirmed by western blot analysis that ICT1 knockdown altered the expression of apoptosis- or cell cycle­related proteins such as Bcl-2, caspase-3, CDK1, CDK2 and cyclin B. In conclusion, targeting ICT1 in breast cancer cells may provide a new strategy for breast cancer gene therapy.