Predicting outcomes of Lung Cancer using the modified glasgow prognostic score: A systematic review and meta-analysis.

Background & Objective: Previous studies have suggested that the modified Glasgow Prognostic Score (mGPS) could be a potential biomarker for lung cancer (LC). However, the association between mGPS and overall survival (OS) or progression-free survival (PFS) in lung cancer patients remains unclear. The purpose of our study was to investigate possible correlation between mGPS and OS or PFS in LC patients. Methods: An extensive search of PubMed, Cochrane Library, EMbase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Trip Database, Worldwide Science, and Google Scholar databases was done for relevant articles, published prior to May 30, 2021, that report correlation between mGPS and OS or PFS in LC patients. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were used as the main parameters for evaluation. Results: A total of 28 studies involving 9,748 lung cancer patients were analysed. The pooled analysis revealed that elevated mGPS (≥ 0) was associated with poor OS (HR=1.54; 95% CI, 1.32-1.77) and PFS (HR=1.49; 95% CI, 1.17-1.82). Furthermore, a significant correlation between mGPS (1 or 2) and OS was observed. However, no significant correlation was found between mGPS (1 or 2) and PFS. Subgroup analysis based on ethnicity demonstrated that mGPS ≥ 0 was associated with worse OS compared to mGPS=0 in both Asian (HR=1.46; 95% CI, 1.04-1.89; p<0.05) and Caucasian (HR=1.64; 95% CI, 1.35-1.94; p<0.05) cohorts of LC patients. Conclusions: Our results demonstrate that positive mGPS is associated with poor survival results. Therefore, mGPS may be used as a biomarker for predicting prognosis in LC patients.

Life quality improvement of patients with non-small cell lung cancer undergoing targeted therapy: A case study of continuous care.

To investigate the improvement effect of targeted therapy on non-small cell carcinoma patients life quality after the continuous nursing intervention. 104 non-small cell lung cancer patients in our hospital from July 2017 to November 2019 were allocated evenly and randomly into the control group (C) and the study group (S). By using clinical baseline data, quality of life questionnaire core 30 for cancer patients, evaluation of patient compliance behavior, the MOS item short-form health survey (SF-36), self rating depression scale (SDS), self rating anxiety scale (SAS), Overall Survival (OS) progression-free survival and adverse reaction symptoms were evaluated for the life quality of patients. There was comparability between the 2 sets of basic data. There was no significant difference in quality of life questionnaire core 30, SF-36, SAS, or SDS scores before treatment. After 3 months, there was a significant difference in the scores of various scales before treatment. At the same time, there was significant statistical significance before and after treatment in Group S. Their compliance rates were 84.62% and 98.08%. Adverse reactions incidence in Group S was lower. Taking a 2-year follow-up period as an example, significant statistical differences existed in OS and progression-free survival rates between adenocarcinoma and squamous carcinoma. SDS and SAS had high consistency in scoring with QLQ-30 and SF-36 scales. Targeted treatment for non-small cell carcinoma patients significantly improves their life quality and reduces the incidence of adverse reactions after continuous nursing intervention.

Antioxidant and anti-inflammatory properties of ginsenoside Rg1 for hyperglycemia in type 2 diabetes mellitus: systematic reviews and meta-analyses of animal studies.

Background: According to existing laboratory data, ginsenoside Rg1 may help cure diabetes and its complications by reducing oxidative stress (OS) and managing inflammation. However, this conclusion lacks reliability and is unclear. As a result, the purpose of this systematic review and meta-analysis was to evaluate the antioxidant and anti-inflammatory effects of ginsenoside Rg1 in the treatment of diabetes and its complications. Methods: We searched for relevant studies published through December 2022, including electronic bibliographic databases such as PubMed, EMBASE, Web of Science, CNKI, and Wanfang. The SYstematic Review Center for Laboratory Animal Experimentation Risk of Bias (SYRCLE RoB) tool was used to conduct a meta-analysis to assess the methodological quality of animal research. The meta-analysis was conducted using RevMan5.4 software, following the Cochrane Handbook for Systematic Reviews of Interventions. This study is registered in the International Systems Review Prospective Registry (PROSPERO) as CRD42023386830. Results: Eighteen eligible studies involving 401 animals were included. Ginsenoside Rg1 was significantly correlated with blood glucose (BG), insulin levels, body weight, superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels. In addition, according to subgroup analysis, the hypoglycemic, anti-inflammatory, and antioxidant effects of ginsenoside Rg1 in type 2 diabetic animals were not affected by experimental species, modeling, experimental drug dosage, or course of treatment. Conclusion: This meta-analysis presents a summary of the hypoglycemic effects of ginsenoside Rg1, which are achieved through anti-inflammatory and antioxidant mechanisms. These findings provide evidence-based support for the medical efficacy of ginsenoside Rg1. Specifically, ginsenoside Rg1 reduced MDA levels and restored SOD activity to exert its antioxidant activity. It had a positive effect on the reduction of IL-6 and TNF-α levels. However, the inclusion of studies with low methodological quality and the presence of publication bias may undermine the validity of the results. Further investigation with a more rigorous experimental design and comprehensive studies is necessary to fully understand the specific glycemic mechanisms of ginsenosides. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier https://CRD42023386830.

Comparative transcriptome profiling analysis provides insight into the mechanisms for sugar change in Chinese jujube (Ziziphus jujuba Mill.) under rain-proof cultivation.

Chinese jujube (Ziziphus jujuba Mill.) is a globally popular and economically important fruit that is rich in bioactive compounds with strong anti-cancer effects. Rain-proof cultivation is widely used to cultivate Chinese jujube, as it helps avoid rainfall damage during fruit harvest. Although the sugar content of jujube fruits differs between rain-proof and open-field cultivation, the underlying molecular mechanisms are unknown. Here, we analyzed the levels of sugar content, sugar accumulation pattern, and transcriptome profiles of jujube fruits at five developmental stages grown under rain-proof and open-field cultivation modes. The sugar content of jujube fruits was significantly higher under rain-proof cultivation than under open-field cultivation, although the sugar composition and sugar accumulation patterns were comparable. Comparative analysis of transcriptomic profiles showed that rain-proof cultivation enhanced the intrinsic metabolic activity of fruit development. Gene expression and correlation analyses suggested that ZjSPS, ZjSS, ZjHXK, and ZjINV regulate the development-related changes in sugar content in jujube fruits grown under rain-proof cultivation. Temperature, humidity, and moisture conditions were key climatic factors affecting sugar accumulation. Our results provide insights into the molecular mechanisms regulating sugar content and sugar accumulation in Chinese jujube fruits grown under rain-proof cultivation, and we provide genetic resources for studying the development mechanism of Chinese jujube fruit.

Cerium End-Deposited Gold Nanorods-Based Photoimmunotherapy for Boosting Tumor Immunogenicity.

BACKGROUND: Triple-negative breast cancer (TNBC) was closely related to high metastatic risk and mortality and has not yet found a targeted receptor for targeted therapy. Cancer immunotherapy, especially photoimmunotherapy, shows promising potential in TNBC treatment because of great spatiotemporal controllability and non-trauma. However, the therapeutic effectiveness was limited by insufficient tumor antigen generation and the immunosuppressive microenvironment. METHODS: We report on the design of cerium oxide (CeO2) end-deposited gold nanorods (CEG) to achieve excellent near-infrared photoimmunotherapy. CEG was synthesized through hydrolyzing of ceria precursor (cerium acetate, Ce(AC)3) on the surface of Au nanorods (NRs) for cancer therapy. The therapeutic response was first verified in murine mammary carcinoma (4T1) cells and then monitored by analysis of the anti-tumor effect in xenograft mouse models. RESULTS: Under near-infrared (NIR) light irradiation, CEG can efficiently generate hot electrons and avoid hot-electron recombination to release heat and form reactive oxygen species (ROS), triggering immunogenic cell death (ICD) and activating part of the immune response. Simultaneously, combining with PD-1 antibody could further enhance cytotoxic T lymphocyte infiltration. CONCLUSIONS: Compared with CBG NRs, CEG NRs showed strong photothermal and photodynamic effects to destroy tumors and activate a part of the immune response. Combining with PD-1 antibody could reverse the immunosuppressive microenvironment and thoroughly activate the immune response. This platform demonstrates the superiority of combination therapy of photoimmunotherapy and PD-1 blockade in TNBC therapy.

Role of Gut Microbiome in Immune Regulation and Immune Checkpoint Therapy of Colorectal Cancer.

Colorectal cancer (CRC) is one of the most frequent gastrointestinal malignant tumors worldwide. Immune checkpoint therapies (ICTs) have been proven to be a reliable treatment for some subtypes of CRC. Gut microbiome is closely involved in intestinal carcinogenesis through the regulation of local immune and inflammation of colonic mucosa. Numerous studies have demonstrated that the immunotherapeutic efficacy of CRC and other kinds of cancer is influenced by the immunosuppressive microenvironment constituted by intestinal microbiome and their metabolites. This Review will discuss the recent advances in how gut microbiome can modify the immune microenvironment and its potential role in ICTs of CRC.

Empyema caused by Eikenella halliae diagnosed by metagenomic next-generation sequencing (mNGS) after pulmonary surgery: A case report.

Background: Empyema is one of the complications of pulmonary surgery for lung cancer, the incidence of which is not very high, but in severe cases, it can even lead to death, and it is always difficult to diagnose the cause by conventional methods. Case presentation: In this study, we report a clinical case of empyema caused by Eikenella halliae after pulmonary surgery in a 55-year-old man. He had a fever, cough, and expectoration for 3 days and was diagnosed with right hydropneumothorax and empyema, pneumonia, postoperative malignant tumor of the right lower lobe (adenocarcinoma), and hypertension. The microbiology laboratory reported Gram-negative bacteria in pleural effusion, which was preliminarily considered as Eikenella based on culture and 16S rRNA sequencing. Furthermore, metagenomic next-generation sequencing (mNGS) of sputum samples was performed two times and reported negative results and the presence of E. halliae, respectively. The pathogen was finally confirmed as E. halliae by whole genome sequencing, suggesting the high-resolution ability of mNGS in the clinical diagnosis of this case. Conclusion: To our knowledge, this is the first case report of E. halliae infection in China, indicating increased pathogenicity of Eikenella sp. in immunocompromised patients, especially after invasive operations. Our findings emphasize that mNGS allows bacterial diagnosis of empyema and can significantly improve the accuracy of the diagnosis.

Comprehensive surgical treatment for obstructive rectal endometriosis: a case report and review of the literature.

BACKGROUND: Intestinal obstruction caused by endometriosis maybe easily misdiagnosed as a tumor or other occupying disease in emergency condition. How to deal with it depending on the clarity of the preoperative diagnosis and the experience of the surgeon. CASE PRESENTATION: A 47-year-old woman, admitted to our emergency service with abdominal pain and distension for 5 days, anal stop exhausting and defecating for 3 days. Based on imaging and laboratory examination, we made a preoperative diagnosis of rectal endometriosis probably. After 7 days of colon decompression with a intestinal obstruction catheter, an operation of laparoscopic partial rectal and sigmoid resection without protective stoma and total hysterectomy was performed successfully. The patient obtained a smooth postoperative course and doing well after 12-weeks follow up. CONCLUSIONS: Obstruction caused by rectal endometriosis is very rare and easily overlooked by surgeon and gynecologist. Appropriate preoperative diagnosis and preoperative management can reduce the trauma and incidence of complications.

The adenosine-A2a receptor regulates the radioresistance of gastric cancer via PI3K-AKT-mTOR pathway.

BACKGROUND: Radiotherapy is a key strategy in gastric cancer (GC) treatment. However, radioresistance remains a serious concern. It is unclear whether the accumulation of adenosine A2a receptor (ADO-A2aR) is related to radioresistance in GC. In this study, the molecular role of ADO-A2aR in GC radioresistance was investigated. METHODS: Colony formation assays were used to assess the role of ADO-A2aR on radioresistance. GC stem cell surface marker expression (including Nanog, OCT-4, SOX-2 and CD44) and PI3K/AKT/mTOR signaling pathway associated protein levels (including phosphorylated PI3K, phosphorylated AKT and phosphorylated mTOR) were determined via western blotting, flow cytometry and immunofluorescence. In addition, the role of ADO-A2aR on radioresistance was explored in vivo using murine xenograft models. RESULTS: ADO-A2aR regulated GC cell stemness both in vitro and in vivo. This was shown to induce radioresistance in GC. ADO-A2aR was revealed to significantly induce cell cycle arrest and promote GC cell apoptosis. These activities were closely linked to activation of the PI3K/AKT/mTOR pathway. CONCLUSION: This study identified that ADO enhances GC cell stemness via interaction with A2aR and subsequent activation of the PI3K/AKT/mTOR pathway. Ultimately, this resulted in radioresistance. A2aR is a potential target to improve GC radiosensitivity.

Effects of the coupling water and fertilizer on soil phosphorus components in alfalfa field in Eastern Inner Mongolia, China.

Soil phosphorus (P) could be categorized into organic and inorganic forms, with diffe-rent capabilities of nutrient supply. Exploring soil P components through liquid 31P-NMR would provide an important theoretical basis for soil P nutrition regulation. This study addressed the characteristic of P in alfalfa (Medicago sativa) soil via the pot experiment. There were two scenarios of treatments with conventional and dry water combined with different P fertilizer levels (P0-P4: 0, 0.025, 0.05, 0.1, and 0.2 g P2O5·kg-1soil). The characteristics of P components in alfalfa soil under water-fertilizer coupling conditions were measured by liquid 31P-NMR. Results showed that under different water and fertilizer treatments, soil inorganic P was mainly composed of inorganic orthophosphate, pyrophosphate and inorganic polyphosphate. Inorganic orthophosphate was the dominant component of inorganic P, which could be reduced by drought. High P application (P4) could increase the contents of soil inorganic polyphosphates and inorganic pyrophosphates. Among the organic P components, monoester orthophosphate was dominant, the conversion and utilization of which in alfalfa soil were affected by drought. Overall, the rational management of water and fertilizer could effectively regulate the conversion and utilization of P nutrients in alfalfa soil in Eastern Inner Mongolia.

BCL11A confers cell invasion and migration in androgen receptor-positive triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is associated with poor clinical prognosis due to a lack of effective therapeutic options. The expression of B-cell lymphoma/leukemia 11A (BCL11A) has been indicated to correlate with TNBC carcinogenesis, though the precise mechanisms of BCL11A-induced tumorigenesis in TNBC remain unclear. Using data retrieved from The Cancer Genome Atlas (TCGA) database, the present study demonstrated that BCL11A expression was upregulated in TNBC, compared with other types of breast cancer. Furthermore, in a tissue microarray of 140 patients with breast cancer, an elevated BCL11A level was correlated with unfavorable overall survival (OS), and exogenous BCL11A-knockdown was subsequently verified to inhibit tumor growth and metastasis in TNBC. Notably, the same tissue microarray revealed that a favorable patient outcome was associated with high expression levels of BCL11A and androgen receptor (AR). Moreover, BCL11A-knockdown significantly inhibited the expression level of AR and further had an influence on proliferation, migration and invasion in TNBC cell lines. Collectively, the results of the current study indicate the function of BCL11A in TNBC progression, and provide new insights into the unique mechanism of BCL11A in AR regulation, emphasizing the significance of more research on BCL11A and AR regulation in TNBC molecular treatment.

A dosimetric study on radiation-induced hypothyroidism following intensity-modulated radiotherapy in patients with nasopharyngeal carcinoma.

The objective of the present study was to investigate the association between thyroid gland-dosimetric parameters and hypothyroidism induced by intensity-modulated radiotherapy in patients with nasopharyngeal carcinoma (NPC). A total of 52 patients with NPC treated in the Department of Radiation Oncology of The Affiliated Hospital of Xuzhou Medical University, from May 2008 to December 2016 were retrospectively enrolled in the present study and divided into two groups based on thyroid function: The euthyroid and hypothyroid groups. The association between hypothyroidism and clinical or dosimetric parameters were analyzed. Females had a significantly increased probability of suffering from radiation-induced hypothyroidism (RIHT), compared with males (P=0.010). The occurrence of RIHT was significantly negatively associated with thyroid volume prior to radiotherapy (P=0.048). Furthermore, the mean dose (Dmean) and V50 in the hypothyroidism group were significantly increased, compared with the euthyroidism group (P=0.017 and P=0.023, respectively). During the treatment optimization period, dose constraints associated with the thyroid gland demonstrated a significantly protective effect on thyroid function compared with the unconstrained group (P=0.034). According to the receiver operating characteristic curves, the threshold value was 5,160 cGy for Dmean and 54.5% for V50. The 3-year cumulative incidence of RIHT was 67.8% when the Dmean value was >5,160 cGy and 44.6% when the Dmean was <5,160 cGy (log rank test, P=0.036). Furthermore, the 3-year cumulative incidence was 66.1% when the V50 was >54.5%, and 29.9% when the V50 was <54.5% (log rank test, P=0.025). In conclusion, RIHT is associated with radiation dose, particularly with Dmean and V50 of the thyroid gland. Dose constraints associated with the thyroid gland significantly reduced the incidence of hypothyroidism compared with the unconstrained group.

Long non-coding RNA FENDRR inhibits cell proliferation and is associated with good prognosis in breast cancer.

INTRODUCTION: FENDRR is a long non-coding RNA (lncRNA) that mediates the modification of the epigenetic landscape of target promoters by binding to polycomb repressive complex 2. However, the role of FENDRR in breast cancer remains unknown. MATERIALS AND METHODS: We detected the expression of FENDRR in 52 breast cancer patients' tissues and five breast cancer cell lines. The association between FENDRR expression and clinicopathological features and prognosis of breast cancer patients was also analyzed. Moreover, cell proliferation assays, flow cytometry analysis, wound-healing assays, and transwell migration assays were performed to detect the biological effects of FENDRR in the breast cancer cells. A xenograft model was used to explore the role of FENDRR expression on tumor growth. RESULTS: We found that FENDRR expression was lower in breast cancer cell lines and cancerous tissues than in the adjacent normal tissues. Low expression of FENDRR was associated with a shorter overall survival and a shorter progression-free survival in breast cancer patients (p<0.001, p<0.001, respectively). We found that FENDRR inhibits breast cancer cell proliferation and migration and promotes cell apoptosis, while FENDRR knockdown promotes breast cancer cell proliferation and migration and suppresses cell apoptosis. Finally, we also detected that FENDRR overexpression could inhibit tumor growth in a xenograft model. CONCLUSION: Our data suggested that FENDRR inhibits breast cancer cell proliferation, promotes cell apoptosis, and is associated with good prognosis in breast cancer. Thus, FENDRR plays an important role in the growth and progression of breast cancer.

ERß1 inhibits metastasis of androgen receptor-positive triple-negative breast cancer by suppressing ZEB1.

BACKGROUND: Increasing evidence has indicated an important role for estrogen receptor beta 1 (ERß1) in breast cancer. However, the role of ERß1 in the metastasis of androgen receptor (AR)-positive triple-negative breast cancer (TNBC) and the underlying mechanisms are still unknown. METHODS: Stable ERß1-expressing TNBC cell lines were generated for this study. We detected the abilities of cell migration and invasion by wound-healing and transwell assays and the expression of E-cadherin and N-cadherin by quantitative RT-PCR (qRT-PCR) and western blotting assays in TNBC cell lines. Chromatin immunoprecipitation (ChIP) analysis was performed to assess the effect of AR on ERß1 promoter. Tumor metastasis was evaluated in vivo using a lung metastasis mouse model. Lastly, immunohistochemical expression of ERß1 in TNBC tissues was analyzed and correlated with clinicopathological features. RESULTS: ERß1 suppressed the invasion and migration abilities of AR-positive TNBC cells and induced the downregulation of ZEB1. ZEB1 overexpression abrogated the increase in E-cadherin expression and the decrease in N-cadherin expression modulated by ERß1. A lung metastasis mouse model showed that the incidence of metastasis was lower in ERß1-expressing TNBC cells. Further, AR activation increased the anti-metastatic effect of ERß1 in AR-positive TNBC cells, which accelerated ERß1 transcription by functioning as a transcription factor that bound to the promoter of ERß1. No significant change was observed in AR expression induced by ERß1. Immunohistochemistry (IHC) analysis of TNBC clinical samples showed that ERß1 and AR were positive in 31.7% and 23.2% of samples, respectively. ERß1 expression was negatively correlated with ZEB1 expression and lymph node metastasis, and positively correlated with the expression of AR and E-cadherin. CONCLUSION: Our findings suggested a potential role of ERß1 in metastasis of AR-positive TNBC and provided novel insights into the mechanism of action of ERß1 and the possible relationship between ERß1 and AR.

Prohibitin promotes androgen receptor activation in ER-positive breast cancer.

Prohibitin (PHB) is an evolutionarily conserved protein with multiple functions in both normal and cancer cells. Androgen receptor (AR) was reported to act as a different role in the ER-positive and ER-negative breast cancer. However, little is known about the role of PHB and whether PHB could regulate AR expression in the ER-positive breast cancer. Here, we determined the expression and clinical outcomes of PHB in breast cancer samples using 121 breast cancer tissues and published databases, and investigated the role of PHB in breast cancer cell growth, apoptosis and cell cycle arrest in the ER-positive breast cancer cells. We obtained the expression of PHB is significantly low in breast cancer samples, and low PHB expression positively correlated with poor prognosis of breast cancer. We detected that PHB could inhibit breast cancer cell proliferation, change cell cycle distribution and promote cell apoptosis in the ER-positive breast cancer cells. Moreover, we found PHB could significantly increase AR expression in both mRNA and protein levels in the ER-positive breast cancer cells. Additionally, a significant positive correlation between PHB and AR expression was identified in the 121 breast cancer tissues. PHB and AR expression are associated with prognosis in the ER-positive breast cancer patients. Our results indicate that PHB promotes AR activation in ER-positive breast cancer, making PHB and AR potential molecular targets for ER-positive breast cancer therapy.

PARP inhibitor increases chemosensitivity by upregulating miR-664b-5p in BRCA1-mutated triple-negative breast cancer.

Emerging evidence has shown that adding poly(ADP-ribose) polymerase (PARP) inhibitors to chemotherapy regimens is superior to the control regimens alone in BRCA1-mutated triple-negative breast cancer (TNBC) patients, but their underlying mechanisms have not been fully elucidated. In this study, using miRNA microarray analysis of two BRCA1-mutated TNBC cell lines, we found that miR-664b-5p expression was increased after adding a PARP inhibitor, olaparib, to a carboplatin (CBP) plus gemcitabine (GEM) therapy regimen. Functional assays showed miR-664b-5p overexpression inhibited proliferation, migration and invasion in BRCA1-mutated TNBC cells. CCNE2 was identified as a novel functional target of miR-664b-5p, and CCNE2 knockdown revealed effects similar to those observed with miR-664b-5p overexpression. Both CCNE2 knockdown and miR-664b-5p overexpression significantly increased the chemosensitivity of BRCA1-mutated TNBC cells. In addition, in vivo studies indicated that miR-664b-5p inhibited tumour growth compared with the control in tumour xenograft models, and we also found that CCNE2 expression was inversely correlated with miR-664b-5p expression in 90 TNBC patient samples. In conclusion, miR-664b-5p functions as a tumour suppressor and has an important role in the regulation of PARP inhibitors to increase chemosensitivity by targeting CCNE2. This may be one of the possible mechanisms by which PARP inhibitors increase chemosensitivity in BRCA1-mutated TNBC.

Antiproliferative Effect of Androgen Receptor Inhibition in Mesenchymal Stem-Like Triple-Negative Breast Cancer.

BACKGROUND/AIMS: Androgen receptor (AR), a steroid hormone receptor, has recently emerged as prognostic and treatment-predictive marker in breast cancer. Previous studies have shown that AR is widely expressed in up to one-third of triple-negative breast cancer (TNBC). However, the role of AR in TNBC is still not fully understood, especially in mesenchymal stem-like (MSL) TNBC cells. METHODS: MSL TNBC MDA-MB-231 and Hs578T breast cancer cells were exposed to various concentration of agonist 5-α-dihydrotestosterone (DHT) or nonsteroidal antagonist bicalutamide or untreated. The effects of AR on cell viability and apoptosis were determined by MTT assay, cell counting, flow cytometry analysis and protein expression of p53, p73, p21 and Cyclin D1 were analyzed by western blotting. The bindings of AR to p73 and p21 promoter were detected by ChIP assay. MDA-MB-231 cells were transplanted into nude mice and the tumor growth curves were determined and expression of AR, p73 and p21 were detected by Immunohistochemistry (IHC) staining after treatment of DHT or bicalutamide. RESULTS: We demonstrate that AR agonist DHT induces MSL TNBC breast cancer cells proliferation and inhibits apoptosis in vitro. Similarly, activated AR significantly increases viability of MDA-MB-231 xenografts in vivo. On the contrary, AR antagonist, bicalutamide, causes apoptosis and exerts inhibitory effects on the growth of breast cancer. Moreover, DHT-dependent activation of AR involves regulation in the cell cycle related genes, including p73, p21 and Cyclin D1. Further investigations indicate the modulation of AR on p73 and p21 mediated by direct binding of AR to their promoters, and DHT could make these binding more effectively. CONCLUSIONS: Our study demonstrates the tumorigenesis role of AR and the inhibitory effect of bicalutamide in AR-positive MSL TNBC both in vitro and in vivo, suggesting that AR inhibition could be a potential therapeutic approach for AR-positive TNBC patients.

p27(Kip1) and Ser10-phosphorylated p27(Kip1) in breast cancer: clinical significance and expression.

BACKGROUND: The protein p27 (p27(Kip1)) is a member of the cyclin-dependent kinase inhibitor family, which negatively regulates cell cycle progression, and the phosphorylation of p27 has been proven to affect its stability and nuclear export. Clinical studies on the relation between p27 and phosphorylated p27 (p-p27Ser10) in breast invasive ductal carcinomas are still scarce. METHODS: We examined the expression of p27 and p-p27Ser10 using immunohistochemistry in 107 breast invasive ductal carcinomas and analyzed the relationship of these biomarkers and tumor characteristics. RESULTS: Of the 107 tumor samples, 38.3% (41 of 107) overexpressed p27 and 64.5% (69 of 107) overexpressed p-p27Ser10. Analysis of correlation with clinical characteristics showed that high expression level of p-p27Ser10 was linked to poor differentiation, advanced disease stage, and lymph node metastasis, whereas a contrary trend was observed for p27 (all P<0.05). In addition, the expression of p-p27Ser10 was significantly higher in malignant tumors than in adjacent tissues, while p27 showed the opposite trend. Also, there were different levels of p27 and p-p27Ser10 in different types of breast cancer. CONCLUSION: p27 and p-p27Ser10 are involved in the development of invasive ductal carcinoma and are potential indicators to judge the degree of malignancy as well as recurrence and metastasis.

[Long-term outcomes of Ahmed glaucoma valve implantation for treating refractory glaucoma].

OBJECTIVE: To explore the efficacies and complications of Ahmed glaucoma valve implantation for treating refractory glaucoma. METHODS: A retrospective study of case series was conducted for 24 patients (26 eyes) with refractory glaucoma from February 2001 to July 2008 at our hospital. Ahmed glaucoma valve implantation was performed. Pre- and post-operative best spectacle-corrected visual acuity (BSCVA), intraocular pressure (IOP), number of medications and complications were recorded and analyzed. The follow-up period was 58-159 months. RESULTS: The post-operative values of IOP were 13.02+/-6.79, 11.43+/-5.24 and 18.56+/-6.43 mmHg at 1 day, 1 month and the last follow-up respectively. There were significant difference when compared with pre-operative IOP (37.59+/-10.76 mmHg, P < 0.01). And 65.38% of eyes maintained or gained ≥ 1 line of BSCVA. But there was no significant difference with pre-operative BSCVA (P = 0.110). Twenty eyes required anti-glaucoma drugs after glaucoma valve implantation and the average number of medication was 1.72+/-0.98. There was significant difference with the pre-operative medication number 2.7 ± 0.7 (P = 0.001). The surgical success rate was 73.1%. And the causes of failure were endophthalmitis, corneal endothelial decompensation, persistent conjunctival wound non-healing, glaucoma valve exposure and loss of light perception.Early postoperative complications were ocular hypotony, shallow anterior chamber, hyphema, transient high IOP and tube occlusion. And long-term complications included encapsulated cyst formation, tube exposure, corneal endothelial decompensation and endophthalmitis. CONCLUSIONS: Ahmed glaucoma valve implantation is efficacious for refractory glaucoma.However, clinicians should pay attention to the prevention and treatment of complications.