Establishing nomograms for predicting disease-free survival and overall survival in patients with breast cancer.

BACKGROUND: Prognostic factors-based nomograms have been utilised to detect the likelihood of the specific cancer events. We have focused on the roles of aldehyde dehydrogenase 1 (ALDH1) and p-AKT in predicting the prognosis of BC patients. This study was designed to establish nomograms based on the integration of aldehyde dehydrogenase 1 (ALDH1) and p-AKT in predicting the disease-free survival (DFS) and overall survival (OS) of breast cancer (BC) patients. METHODS: Demographic and clinical data were obtained from BC patients admitted to our hospital between September 2015 and August 2016. Univariate and multivariate Cox regression analyses were utilised to analyse the risk factors of recurrence and mortality. The nomograms for predicting the DFS and OS were established using the screened risk factors. Stratified analysis was performed with the cut-off value of exp (pi) of 4.0-fold in DFS and OS, respectively. RESULTS: Multivariate Cox regression analysis indicated that ALDH, p-AKT and pathological stage III were independent risk factors for the recurrence among BC patients. ALDH1, p-AKT, pathological stage III and ER-/PR-/HER2- were independent risk factors for the mortality among BC patients. The established nomograms based on these factors were effective for predicting the DFS and OS with good agreement to the calibration curve and acceptable area under the receiver operating characteristic (ROC) curve. Finally, stratified analyses showed patients with a low pi showed significant decrease in the DFS and OS compared with those of high risk. CONCLUSION: We established nomograms for predicting the DFS and OS of BC patients based on ALDH1, p-AKT and pathological stages. The ER-/PR-/HER2- may be utilised to predict the OS rather than DFS in the BC patients.

Many breast cancer patients show poor response after treatment due to recurrence and metastasis. Therefore, early prediction of the disease-free survival and overall survival is crucial to the treatment outcome and clinical decision-making. In this study, we established nomograms with the demographic and clinical data from breast cancer patients admitted to our hospital between September 2015 and August 2016. Univariate and multivariate Cox regression analyses showed that some important proteins and signalling pathways were risk factors for decreased disease-free survival and overall survival of breast cancer patients. On this basis, we established an effective nomogram for predicting the disease-free survival and overall survival of these patients based on these factors. This study offers new options in the predicting the treatment outcome of breast cancer patients.

Investigation of BRAF mutation in a series of papillary thyroid carcinoma and matched-lymph node metastasis with ARMS PCR.

OBJECTIVES: To figure out that if there is a consistency relationship of the BRAFV600E mutation in matched-lymph node metastasis and original papillary thyroid carcinoma (PTC) specimen for the same patient. METHODS: We collected the specimen of thyroids and matched-lymph node metastases of PTCs and tested the BRAFV600E mutation status with amplification refractory mutation system (ARMS) PCR. RESULTS: 20 patients with PTC and metastasis lymph node were hired. In this cohort, 16 (80%) patients had the same BRAF genetic mutation status in thyroid and metastasis, and the other 4 (20%) had an inconsistent situation. CONCLUSIONS: Within our cohort, the data suggested that wild-type BRAFV600E oncogene in thyroid primary tumor does not rule out its mutation in lymph node metastasis, and vice versa.

Expression of pAkt is associated with a poor prognosis in Chinese women with invasive ductal breast cancer.

Over the past three decades, numerous patients with breast cancer succumbed to cancer metastasis and recurrence, while, the exact mechanisms underlying this malignancy, and the potential biomarkers for prognosis prediction remain elusive. It was previously demonstrated that phosphorylated RAC-α serine/threonine-protein kinase (pAkt) and Beclin 1 was associated with cancer metastasis, and recurrence. Thus far, the expression patterns of pAkt and Beclin 1 in breast cancer tissues, and their associations with the prognosis of invasive ductal breast cancer remain inconclusive, which may be due to various factors, including ethnicity and pathological types. In the present study, a total of 90 Chinese female patients with invasive ductal breast cancer between June 1999 and August 2002 were enrolled at Shanghai First People's Hospital (Shanghai, China). The patients were followed up from 5 months to 13.5 years for survival analysis. The expressional levels of pAkt and Beclin 1 in invasive ductal breast cancer tissues, and the normal paracancerous tissues were measured by immunohistochemistry. Associations with prognosis following surgery were further evaluated using Cox regression analysis. In 90 invasive ductal breast cancer samples, pAkt was detected in 17 (18.9%) samples and Beclin 1 in 33 (36.7%) samples, but both were not detected in any of the paracancerous samples. Survival analysis revealed that pAkt expression carried a tendency to predict a shorter disease-free survival (DFS) in patients with invasive ductal breast cancer. Additionally, Beclin 1 expression was not significantly associated with survival. Furthermore, univariate Cox regression analysis demonstrated that pAkt expression was negatively associated with DFS and overall survival. Multivariate Cox regression analysis indicated that pAkt expression was an independent risk factor associated with poor prognosis in patients with invasive ductal breast cancer (all P<0.05). pAkt may be used as a potential prognostic biomarker in Chinese women with invasive ductal breast cancer.

Shikonin suppresses pulmonary fibroblasts proliferation and activation by regulating Akt and p38 MAPK signaling pathways.

Fibroblast is believed to be the primary effector in idiopathic pulmonary fibrosis (IPF), a progressive lung disorder characterized by aberrant tissue remodeling and the formation of fibroblastic foci. Due to the complicated etiology and mechanism, there are few effective drugs for this fatal disease. Shikonin (SHI), which is the major ingredient isolated from the plant Lithospermum Erythrorhizon, has long been used as traditional medicine for many diseases including inflammation and cancer. The roles of SHI in attenuating skin scar and renal fibrosis by reducing TGFß1-stimulated fibroblast activation are also reported. But whether SHI works on IPF which exhibits both inflammatory and carcinoma-like features remains unknown. In this study, using isolated pulmonary fibroblasts, we demonstrated that SHI inhibited the proliferation, migration of fibroblasts, enhanced cell apoptosis and led to cell cycle arrest at G1 and G2/M phase. Moreover, SHI reduced the production of α-SMA, fibronectin, collagen I and III in response to TGF-ß induction in pulmonary fibroblasts, and all of these gene production is the key component of extracellular matrix for tissue remodeling for IPF. The phosphorylation of Akt was down-regulated, p53 increased, the mRNA levels of p21 and p27 enhanced after SHI treatments. The phosphorylation of both p38 MAPK and Akt stimulated by TGF-ß was reduced after SHI treatments. Collectively, these data indicate that SHI has a strong cytotoxicity in pulmonary fibroblast via inhibiting Akt activation signaling pathway, and attenuates TGF-ß induced extracellular matrix genes production in pulmonary fibroblasts via modulating the activities of p38 MAPK and Akt. SHI might serve as a therapeutically candidate for IPF patients.

Use of aprotinin to reduce blood loss and transfusion in major orthopedic surgery: a meta-analysis.

BACKGROUD: Conflicting reports have been published regarding the effectiveness and safety of aprotinin in reducing blood loss and transfusion in patients undergoing orthopedic surgery. We performed a meta-analysis to evaluate the effectiveness and safety of aprotinin in reducing blood loss and transfusion in major orthopedic surgery. MATERIALS AND METHODS: MEDLINE, PubMed, EMBASE and Cochrane databases were searched for relevant studies. Only randomized controlled trials were eligible for this study. The weighted mean difference in blood loss, and number of transfusions per patient and the summary risk ratio of transfusion requirements, and deep-vein thrombosis (DVT) were calculated in the aprotinin-treated group and the control group. RESULTS: Eighteen randomized controlled trials involving 1276 patients were included. The use of aprotinin reduced total blood loss by a mean of 498.88 ml (95% confidence interval [CI]; -735.03 to -262.72), intra-operative blood loss by a mean of 246.11 ml (95% CI; -352.11 to -140.11), post-operative blood loss by a mean of 169.11 ml (95% CI; -234.06 to -105.55), the number of blood transfusions per patient by 0.93 units (95% CI; -1.36 to -0.51). Aprotinin led to a signficant reduction in transfusion requirements (RR 0.59; 95% CI; 0.51 to 0.69) and no increase in the risk of DVT (RR 0.58; 95% CI; 0.38 to 1.08). CONCLUSION: The meta-analysis shows that aprotinin could significantly reduce blood loss and blood transfusion requirements in patients undergoing orthopedic surgery, and it did not appear to increase the risk of DVT.

MCF-7/ADR cells (re-designated NCI/ADR-RES) are not derived from MCF-7 breast cancer cells: a loss for breast cancer multidrug-resistant research.

MCF-7/ADR cells have been widely used as a multidrug-resistant breast cancer cell model in cancer research. The origin of MCF-7/ADR has been a matter of debate since MCF-7/ADR cells were re-designated NCI/ADR-RES in 1998. Many recent studies still describe MCF-7/ADR cells as originating from the breast cancer cell line MCF-7. Thus, the real origin of MCF-7/ADR cells remains more unclear. In this study, a new adriamycin (ADR)-resistant cell line MCF-7/ADR' was reproduced using the same procedure employed during the initial establishment of MCF-7/ADR. Since the MCF-7/ADR' cell line was definitely derived from parental MCF-7 cells, we were able to directly compare these cell lines together with MCF-7/ADR using immunocytochemical, morphological, and consecutive DNA fingerprinting analyses to determine the true origin of MCF-7/ADR. Both ADR-resistant cell lines displayed some similar phenotypic characteristics, such as high levels of P-glycoprotein (P-gp) expression, increased vacuolation, abundant filamentous material, and irregular pseudopodia. With increasing concentrations of ADR, the DNA fingerprints of MCF-7/ADR' cells were always identical to the parental MCF-7 cells. However, the DNA fingerprints of MCF-7/ADR cells did not relate to MCF-7 or MCF-7/ADR'. MCF-7/ADR and the breast cancer cell line MCF-7 are not of the same origin. Long-time culture in the presence of ADR does not cause significant changes in DNA fingerprint patterns.