Low pretreatment prognostic nutritional index predicts poor survival in breast cancer patients: A meta-analysis.

BACKGROUND: Prognostic nutritional index (PNI), as an indicator of nutritional immune status, has been shown to be associated with therapeutic effects and survival of solid tumors. However, the prognostic role of PNI before treatment in human breast cancer (BC) is still not conclusive. Hence, we performed this meta-analysis to assess the value of it in prognosis prediction for BC patients. MATERIALS AND METHODS: We searched PubMed, Embase, Web of Science and EBSCO to identify the studies evaluating the association between PNI and survival such as overall survival (OS), disease-free survival (DFS) of BC, and computed extracted data into hazard ratios (HRs) for OS, DFS and clinicopathological features with STATA 12.0. RESULTS: A total of 2322 patients with BC from 8 published studies were incorporated into this meta-analysis. We discovered that low pretreatment PNI was significantly associated with worse OS, but not with DFS in BC patients. In stratified analyses, the result showed that decreased PNI before treatment was remarkably related with lower 3-year, 5-year, 8-year and 10-year OS, but not with 1-year survival rate in BC. In addition, although reduced PNI could not impact 1-year, 3-year or 5-year DFS, it considerably deteriorated 8-year and 10-year DFS in patients. CONCLUSION: Low pretreatment PNI deteriorated OS, 8-year and 10-year DFS in BC patients, implicating that it is a valuable prognostic index and improving the nutritional immune status may offer a therapeutic strategy for these patients.

LAG-3+ tumor-infiltrating lymphocytes ameliorates overall survival in triple-negative breast cancer patients.

Purpose: Immune checkpoint molecule lymphocyte-activating gene-3 (LAG-3), which is expressed on active lymphocytes, has proven to be associated with immunosuppression and cancer progression in a variety of solid tumors. However, the role of LAG-3+ lymphocytes in human breast cancer (BC) is still not conclusive. We therefore performed a meta-analysis to clarify the role of these cells in prognosis prediction for BC. Methods: We searched PubMed, Embase, and EBSCO to identify the studies evaluating the association of LAG-3+ lymphocyte infiltration and overall survival (OS) and/or disease-free survival (DFS) in BC patients, then combined extracted data with STATA 12.0. Results: Eight published studies involving 5,859 BC patients were incorporated into this meta-analysis. We noted that a high number of LAG-3+ tumor-infiltrating lymphocytes were not appreciably associated with OS and DFS in BC patients. Strikingly, in stratified analyses based on the molecular type of BC, LAG-3+ lymphocyte infiltration was remarkably associated with better OS rather than DFS in triple-negative breast cancer (TNBC), whereas it significantly influenced neither OS nor DFS in Her2-positive BC. However, an increased density of these lymphocytes indicated a trend for better OS in Her2-positive BC. In addition, we found that LAG-3+ lymphocyte infiltration was also remarkably associated with prolonged OS in Her2-positive BC patients when they were measured by immunohistochemistry (IHC). In addition, an elevated number of these lymphocytes did not correlate with pathological complete response rate or clinicopathological features including lymph node metastasis. Conclusion: The infiltration of LAG-3+ lymphocytes ameliorates OS in TNBC and Her2-positive BC, implicating that it is a valuable prognostic biomarker, and applications of anti-LAG-3 antagonists may possibly be not a promising therapeutic strategy for human BC especially for TNBC.

Declining human activity intensity on alpine grasslands of the Tibetan Plateau.

Climate change and human activities have profoundly changed the structure and functioning of alpine grassland ecosystems on the Tibetan Plateau, the most critical ecological safety shelter for Asia. However, it remains unclear to what degree human activity intensity has impacted the alpine grasslands of the Tibetan Plateau. Here we quantify human activity intensity on alpine grasslands of the Tibetan Plateau based on the relationship between actual and potential net primary production. We found that human activity intensity decreased by 16.1% from 2000 to 2017 across the alpine grasslands, which might be driven by recent ecological conservation policies, especially reductions in livestock numbers. Critical thresholds, which show marked grassland responses to different levels of human disturbances, were identified for each ecozone. The net primary production of dry grasslands on the western ecozones was more resistant to human disturbances but with lower resilience than other alpine grasslands on the plateau. Our findings are beneficial to design practical countermeasures to adapt to climate change and recover damaged grasslands on Tibetan Plateau.

An IL6-Adenosine Positive Feedback Loop between CD73+ γδTregs and CAFs Promotes Tumor Progression in Human Breast Cancer.

The tumor microenvironment induces immunosuppression via recruiting and expanding suppressive immune cells such as regulatory T cells (Treg) to promote cancer progression. In this study, we documented that tumor-infiltrating CD73+ γδTregs were the predominant Tregs in human breast cancer and exerted more potent immunosuppressive activity than CD4+ or CD8+ Tregs. We further demonstrated that cancer-associated fibroblast (CAF)-derived IL6, rather than TGFß1, induced CD73+ γδTreg differentiation from paired normal breast tissues via the IL6/STAT3 pathway to produce more adenosine and become potent immunosuppressive T cells. CD73+ γδTregs could in turn promote IL6 secretion by CAFs through adenosine/A2BR/p38MAPK signaling, thereby forming an IL6-adenosine positive feedback loop. CD73+ γδTreg infiltration also impaired the tumoricidal functions of CD8+ T cells and significantly correlated with worse prognosis of patients. The data indicate that the IL6-adenosine loop between CD73+ γδTregs and CAFs is important to promote immunosuppression and tumor progression in human breast cancer, which may be critical for tumor immunotherapy.

Cellular immunotherapy plus chemotherapy ameliorates survival in gastric cancer patients: a meta-analysis.

The efficacy of cellular immunotherapy plus chemotherapy in treatment of gastric cancer (GC) remains inconsistent even controversial. Hence, we performed a meta-analysis to better comprehend the clinical value of cellular immunotherapy plus chemotherapy for GC patients. We searched PubMed, Embase and EBSCO databases to identify the studies evaluating the association of cellular immunotherapy plus chemotherapy and overall survival (OS) and/or disease-free survival (DFS) in patients with GC, and then combined relevant data into hazard ratios (HRs) for OS, DFS and clinicopathological features such as TNM stage, etc. with STATA 12.0. Eleven studies with 1244 patients were included in this meta-analysis. We found that cellular immunotherapy plus chemotherapy remarkably improved overall survival (OS) and diseases-free survival (DFS) as compared to the chemotherapy for GC patients. In subgroup analyses, pooled data showed that the combined therapy was significantly associated with better 3-year and 5-year survival rate, but not with 1-year survival rate of patients; the application of cellular immunotherapy based on either CIK or DC-CIK cells could enhance survival as well as NK, γδT and CIK cells-based immunotherapy. More importantly, the addition of cellular immunotherapy considerably improved OS and DFS only in patients with stage III rather than stage II. In addition, we also discovered that the combined therapy did not cause intolerable side effects to patients. Cellular immunotherapy plus chemotherapy ameliorates survival in GC, especially in patients with stage III, implicating that it is a valuable therapeutic strategy for these patients.

Tumor-Infiltrating Podoplanin+ Fibroblasts Predict Worse Outcome in Solid Tumors.

BACKGROUND/AIMS: Tumor-infiltrating fibroblasts are a heterogeneous population, and different subpopulations play differential roles in tumor microenvironment. However, the prognostic role of podoplanin+ fibroblasts in human solid tumors still remains controversial. Therefore, we performed the meta-analysis to better understand the role of this subpopulation in prognosis prediction for patients with solid tumor. METHODS: We searched PubMed and EBSCO to identify the studies evaluating the association of intratumoral podoplanin+ fibroblast density detected by immunohistochemical method and overall survival (OS) and/or disease-free survival (DFS) in patients with solid tumor, then computed extracted data into hazard ratios for OS, DFS and clinicopathological features with STATA 12.0. RESULTS: A total of 4883 patients from 29 published studies were incorporated into this meta-analysis. We found that podoplanin+ fibroblast infiltration significantly decreased OS and DFS in all types of solid tumors. In stratified analyses, podoplanin+ fibroblast infiltration was significantly associated with worse OS in cholangiocarcinoma, breast, lung and pancreatic cancer. And these cells were inversely associated with DFS in breast, lung and pancreatic cancer. In addition, high density of these cells significantly correlated with unfavorable clinicopathological features such as lymph node metastasis, TNM stage, lymphatic and vascular invasion of solid tumor. CONCLUSION: Podoplanin+ fibroblast infiltration leads to worse clinical outcome in solid tumors, implicating that it is a valuable prognostic biomarker and targeting it may have a potential for effective treatment.

The potential of microRNAs as human prostate cancer biomarkers: A meta-analysis of related studies.

Prostate cancer (PC) is a very important kind of male malignancies. When PC evolves into a stage of hormone resistance or metastasis, the fatality rate is very high. Currently, discoveries and advances in miRNAs as biomarkers have opened the potential for the diagnosis of PC, especially early diagnosis. miRNAs not only can noninvasively or minimally invasively identify PC, but also can provide the data for optimization and personalization of therapy. Moreover, miRNAs have been shown to play an important role to predict prognosis of PC. The purpose of this meta-analysis is to integrate the currently published expression profile data of miRNAs in PC, and evaluate the value of miRNAs as biomarkers for PC. All of relevant records were selected via electronic databases: Pubmed, Embase, Cochrane, and CNKI based on the assessment of title, abstract, and full text. we extracted mean ± SD or fold change of miRNAs expression levels in PC versus BPH or normal controls. Pooled hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS) and recurrence-free survival (RFS), were also calculated to detect the relationship between high miRNAs expression and PC prognosis. Selected 104 articles were published in 2007-2017. According to the inclusion criteria, 104 records were included for this meta-analysis. The pooled or stratified analyze showed 10 up-regulated miRNAs (miR-18a, miR-34a, miR-106b, miR-141, miR-182, miR-183, miR-200a/b, miR-301a, and miR-375) and 14 down-regulated miRNAs (miR-1, miR-23b/27b, miR-30c, miR-99b, miR-139-5p, miR-152, miR-187, miR-204, miR-205, miR-224, miR-452, miR-505, and let-7c) had relatively good diagnostic and predictive potential to discriminate PC from BPH/normal controls. Furthermore, high expression of miR-32 and low expression of let-7c could be used to differentiate metastatic PC from local/primary PC. Additional interesting findings were that the expression profiles of five miRNAs (miR-21, miR-30c, miR-129, miR-145, and let-7c) could predict poor RFS of PC, while the evaluation of miR-375 was associated with worse OS. miRNAs are important regulators in PC progression. Our results indicate that miRNAs are suitable for predicting the different stages of PC. The detection of miRNAs is an effective way to control patient's prognosis and evaluate therapeutic efficacy. However, large-scale detections based on common clinical guidelines are still necessary to further validate our conclusions, due to the bias induced by molecular heterogeneity and differences in study design and detection methods.

Comparison of the hemodynamics and dynamics of fluid shift of Ringer's solution before surgery in children and adults.

The present study investigated the hemodynamics, vascular and extravascular volume expansion induced by infusion of lactated Ringer's solution in children and adults before surgery. This was a prospective randomized double-blind study. A total of 28 patients (14 children and 14 adult patients; American Society of Anesthesiology status I) scheduled for similar minor pelvic, anal rectal or lower limb surgery were recruited for the present study. All patients were administered with 10 ml/kg of lactated Ringer's solution at a constant rate over 20 min. After fluid infusion, plasma dilutions were calculated based on the concentration of hemoglobin. Heart rate (HR), mean arterial pressure (MAP) and urine output were measured before anesthesia was administered for surgery. Results demonstrated that the plasma dilution within 90 min of infusion initiation of lactated Ringer's solution was less pronounced in children compared with adult patients (0.07 vs. 0.16; P<0.001). Children also excreted more of the infused fluid through the kidney within 90 min of infusion initiation than the adults (55% vs. 24%; P=0.01). Following completion of fluid infusion, the volume expansion efficiency was higher in adults [0.82 (0.52-1.00)] than in children [0.46 (0.26-0.68)]. The relative changes in HR were significantly greater in children than in adults 15-60 min after infusion initiation (P<0.01). After 60 min, HRs were comparable between the groups; however, MAP declined significantly from 25-90 min after infusion initiation in children (P<0.05), yet remained nearly constant in adults (P>0.05). Simple regression analysis revealed a positive relationship between the relative changes in MAP and the plasma dilution, and the reduction in MAP in children was able to explain 47% of the variation in plasma dilution (R2=0.47; P=0.007). In conclusion, different hemodynamics and dynamics of fluid shift of Ringer's solution prior to surgery in children and adults may provide anesthesiologists with new information of how to administer fluid treatment for each patient.

Poly(glucono-δ-lactone) based nanocarriers as novel biodegradable drug delivery platforms.

Novel biocompatible and biodegradable polymers are highly desirable and crucial in drug delivery applications in order to overcome the technical challenges and problems existing in the traditional method of poly(ethylene glycol) based drug carriers. In this study, ring-opening polymerization of a carbohydrate-derived lactone, glucono-δ-lactone (GDL), generates a new highly branched polymer (PGDL) that can form stable nanoparticles through a w/o emulsification approach. The biodegradable and biocompatible particles can carry anticancer agent 5-fluorouracil (5-FU) effectively. The controlled release of 5-FU from the PGDL particles exhibits a non-Fickian mechanism without an initial burst, with an enhanced release exponent at tumoral pH. Cell viability studies by MTT assays indicate that ovarian carcinoma cells (OVCAR-3) and macrophage cells (raw 264.7) treated with PGDL (2.5mg/ml) show no signs of toxicity in 24h cell incubations. The PGDL particles can interact with the OVCAR-3 cell line efficiently. Therefore, the glucono-δ-lactone based particles represent an effective delivery system for cancer therapy.

[Comparative study on the protein maps of different parts of Cervus nippon antler by two-dimensional electrophoresis].

OBJECTIVE: To optimize the two-dimensional electrophoresis (2-DE) method for the proteome analysis of the Cervus nippon antler, and compare the protein maps of different parts of Cervus nippon antler. METHODS: The total proteins of Cervus nippon antler were extracted by protein lysate containing 7 mol/L Urea, 4% CHAPS, 2 mol/L Thiourea, 65 mmol/L DTT, 1 mmol/L PMSF and 0.2% Bio-Lyte. The proteins were separated by immobilized pH 3 - 10 linear gradient (IPG), 7 cm strips as the first dimension. Isoelectric focusing conditions were optimized. 12% SDS-PAGE was used as the second dimension electrophoresis. The gels were stained with Coomassie brilliant blue and analyzed by PDQuest analysis software. RESULTS: The contents of total protein and the numbers of protein points of three different parts of Cervus nippon antler reduced gradually from the top to the bottom. Comparing three maps of different parts of Cervus nippon antler, there were 18 different protein points. Isoelectric point, molecular weight and gray value of each different protein point were calculated. CONCLUSION: An optimized two-dimensional electrophoresis method for the proteome analysis of the Cervus nippon antler is established. The 2-DE profiles of different parts of Cervus nippon antler exist obvious differences. The different protein points can be used as reference for Cervus nippon antler quality control and evaluation.